The space shuttle was able to land on a runway like an aircraft, while the Russian Soyuz vehicle parachutes down to the Kazakh steppe. But the Crew Dragon will land on water - in the Atlantic Ocean.
Astronauts have not splashed down in a capsule since the days of the Apollo missions to the Moon in the 1960s and 70s.
Here's an illustration showing how the SpaceX vehicle will return from the International Space Station.
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Artwork joins the astronauts
Dragon is carrying two special items in addition to its astronauts.
One is a series of custom art pieces by a Los Angeles artist entitled "humankind". The indestructible paintings, meant to celebrate humanity, are made from gold, brass and aluminum. They also pay homage to the Saturn V rocket as well as the SpaceX Falcon 9 launcher.
A mosaic image of Earth, comprised of over 100,000 photos of 2020 graduates from around the world, is also travelling up with the astronauts.
NasaCopyright: Nasa
A welcome from 250 miles above
Nasa astronaut Chris Cassidy, the lone American aboard the ISS, is ready and waiting to welcome Hurley and Behnken tomorrow if lift-off happens today.
From 250 miles (402km) above the Earth, he says he's excited about the launch and to welcome "two close friends" to the station.
He's flown with Hurley before on shuttle missions, but this is his first mission with Behnken.
"I can't wait to look out the window and see my friends on close approach," Cassidy says.
"Go Falcon 9, go Dragon, and go Bob and Doug. I'll see you soon."
NasaCopyright: Nasa
The mission in graphics
BBCCopyright: BBC
Some details about what's going to happen on this mission.
Hurley's and Behnken's lift-off from the Kennedy Space Center is scheduled for 16:33 local time (20:33 GMT / 21:33).
Their ascent to orbit should take a little under nine minutes. A series of further manoeuvres will see the men's capsule dock with the ISS on Thursday at 15:29 GMT (16:29 BST).
It's unclear at the moment how long they'll spend on the orbiting outpost before coming home, but it's likely to be just short of four months.
Air Force One approaches
NasaCopyright: Nasa
President Donald Trump, aboard Air Force One, is approaching the space centre.
Ahead of landing, the presidential aeroplane has just flown over the historic launch pad.
The last US president to witness a launch from the centre was Bill Clinton in October 1998, according to Nasa.
Hatch closed
The astronauts are seated properly, the hatch has been closed, and more communications checks are underway.
The crew has just finished an important hatch leak check as well, meaning most of their duties are complete.
If weather permits, we've got less than two hours to go until lift-off.
NasaCopyright: Nasa
New suits to reignite 'the dream of space'
Getty ImagesCopyright: Getty Images
Behnken (right) and Hurley (left) in the new suitsImage caption: Behnken (right) and Hurley (left) in the new suits
Musk answers a question from social media about the futuristic suits.
He says he spent a lot of time personally working on the design, and ultimately, it took nearly four years to successfully blend form and functionality.
But why the emphasis on looks?
"We want to inspire kids to say one day they want to wear that uniform," Musk says.
"Get them fired up about, 'yeah I want to be an astronaut, I want to work on aerospace engineering, I want to advance space flight'.
"What today is about is reigniting the dream of space," Musk emphasises. He adds that everyone, all over the world, should be "excited that this is a thing that is made by humans for humans".
Bridenstine adds: "If we can get Tom Cruise to inspire an elementary kid to join the Navy and be a pilot, why cant we get Tom Cruise to inspire the next Elon Musk?"
He says "we need a new generation of many Elon Musks and that's what this launch is about today".
'Done everything to make sure dad's coming back'
Musk says the upcoming launch is "the result of thousands of tests, thousands of design hours and a tremendous number of smart people working incredibly hard to make this day happen".
When asked about the responsibility he feels towards the astronatus, Musk says he felt it "most strongly when I saw their family just before coming here".
"I said we've done everything we can to make sure your dad's coming back."
Getty ImagesCopyright: Getty Images
Hurley's family says goodbye to him before he boards the craftImage caption: Hurley's family says goodbye to him before he boards the craft
'This is a dream come true'
"We've had challenges, we've had setbacks, catastrohpic losses of capsules...but that's what's unique about SpaceX," Nasa administrator Jim Bridenstine says, adding that the private company can do things Nasa historically hasn't been able to do.
Elon Musk interjects momentarily to note that the setbacks have all been in uncrewed tests, on the ground.
"They test, they fail, they fix, they fly...until the point where we are today," Bridenstine says.
Musk says: "This is a dream come true."
He added: "When starting SpaceX in 2002, I really did not think this day would occur. I expected 90% chance we'd fail to get to low-Earth orbit with a small rocket.
"So if somebody told me in 2002 I'd be standing here with the Nasa administrator, meeting the astronauts and that we had a rocket and spacecraft on Pad 39A... I'd have thought, man I don't know what you're smoking, but - no way is that true."
NasaCopyright: Nasa
How's the weather?
Getty ImagesCopyright: Getty Images
The crew is still monitoring the weather, but so far the launch is still on. Stormy clouds and fog have surrounded the centre since this morning.
The crew just finished a number of communications checks with the launch director and teams on the ground, and the astronauts are all buckled in now.
NASACopyright: NASA
NasaCopyright: Nasa
Launching amid a pandemic
In the past, such launches saw hundreds of thousands of Americans turn up to the Florida space centre to watch liftoff.
But this year, Covid-19 precautions mean things will look very different.
Only a limited number of staff and officials will be attending the launch, and visitors have been discouraged by Nasa and SpaceX.
The Kennedy Space Center remains closed to the public today, but is due to open to limited numbers on Thursday.
Nasa administrator Jim Bridenstine has asked members of the public to watch the launch online or on television instead, and the agency has publicised its various social media platforms where people can engage with the event.
But Brevard County Sheriff Wayne Ivey on Friday encouraged residents to watch the launch, telling reporters: “If Nasa is telling people to not come here and watch the launch, that’s on them. I’m telling people what I believe as an American.”
Local media say there are already some crowds forming in nearby parks and restaurants to watch the historic launch.
Test your own piloting skills
Earlier this month, SpaceX released an online simulator that lets anyone try their hand at piloting the Dragon 2 craft and docking with the space station.
While we wait for this afternoon's launch, you can have a go at steering the craft with its many controls on the SpaceX site, here.
Astronauts enter the capsule
Hurley and Behnken are inside the Dragon capsule - a few minutes ahead of schedule. Technicians are now strapping them in and checking suits.
They'll also again check two-way communications systems between the astronauts and crew.
NASACopyright: NASA
Signing the white room wall
Next step: ingress. That's the term for when they climb into the Dragon craft.
As they enter the white room, a sealed off, clean space at the end of the crew access arm that's the last place the astronauts see on earth, they've started a new tradition: signing the wall of the white room.
NASACopyright: NASA
Going up
Hurley and Behnken are heading up via a quick elevator ride to Level 255 - 255ft (77m) up. From there, they'll walk upstairs to level 265, where the crew access area awaits.
NASACopyright: NASA
At the pad
The gull-winged Teslas have pulled up at the pad. Hurley and Behnken will now take the lift up the service tower to get into their capsule.
NASACopyright: NASA
In convoy
The astronauts are in their Tesla motors and are driving down to Launch Complex 39A. Waiting is their Falcon-9 rocket and Crew Dragon capsule.
NASACopyright: NASA
NASACopyright: NASA
The famous walk-out
We haven't seen this for nine years - not since the last shuttle mission. Doug Hurley and Bob Behnken walk out to the vehicles that will drive them down to the pad. A last (virtual) hug with the kids.
NASACopyright: NASA
How we got to this point
Paul Rincon
Science editor, BBC News website
SpaceXCopyright: SpaceX
Crew DragonImage caption: Crew Dragon
Why is SpaceX launching astronauts to the International Space Station for Nasa?
It all goes back to a tragic accident: the loss of the space shuttle Columbia in 2003. That triggered a dramatic shift in direction for America's human spaceflight programme.
President George W Bush decided to retire the shuttle and build a new space vehicle capable of reaching the Moon.
This opened up commercial opportunities for the routine transportation of cargo and astronauts to low-Earth orbit.
Live Reporting
Ritu Prasad, Jonathan Amos and Paul Rincon
All times stated are UK
How the Crew Dragon returns from space
The space shuttle was able to land on a runway like an aircraft, while the Russian Soyuz vehicle parachutes down to the Kazakh steppe. But the Crew Dragon will land on water - in the Atlantic Ocean.
Astronauts have not splashed down in a capsule since the days of the Apollo missions to the Moon in the 1960s and 70s.
Here's an illustration showing how the SpaceX vehicle will return from the International Space Station.
Artwork joins the astronauts
Dragon is carrying two special items in addition to its astronauts.
One is a series of custom art pieces by a Los Angeles artist entitled "humankind". The indestructible paintings, meant to celebrate humanity, are made from gold, brass and aluminum. They also pay homage to the Saturn V rocket as well as the SpaceX Falcon 9 launcher.
A mosaic image of Earth, comprised of over 100,000 photos of 2020 graduates from around the world, is also travelling up with the astronauts.
A welcome from 250 miles above
Nasa astronaut Chris Cassidy, the lone American aboard the ISS, is ready and waiting to welcome Hurley and Behnken tomorrow if lift-off happens today.
From 250 miles (402km) above the Earth, he says he's excited about the launch and to welcome "two close friends" to the station.
He's flown with Hurley before on shuttle missions, but this is his first mission with Behnken.
"I can't wait to look out the window and see my friends on close approach," Cassidy says.
"Go Falcon 9, go Dragon, and go Bob and Doug. I'll see you soon."
The mission in graphics
Some details about what's going to happen on this mission.
Hurley's and Behnken's lift-off from the Kennedy Space Center is scheduled for 16:33 local time (20:33 GMT / 21:33).
Their ascent to orbit should take a little under nine minutes. A series of further manoeuvres will see the men's capsule dock with the ISS on Thursday at 15:29 GMT (16:29 BST).
It's unclear at the moment how long they'll spend on the orbiting outpost before coming home, but it's likely to be just short of four months.
Air Force One approaches
President Donald Trump, aboard Air Force One, is approaching the space centre.
Ahead of landing, the presidential aeroplane has just flown over the historic launch pad.
The last US president to witness a launch from the centre was Bill Clinton in October 1998, according to Nasa.
Hatch closed
The astronauts are seated properly, the hatch has been closed, and more communications checks are underway.
The crew has just finished an important hatch leak check as well, meaning most of their duties are complete.
If weather permits, we've got less than two hours to go until lift-off.
New suits to reignite 'the dream of space'
Musk answers a question from social media about the futuristic suits.
He says he spent a lot of time personally working on the design, and ultimately, it took nearly four years to successfully blend form and functionality.
But why the emphasis on looks?
"We want to inspire kids to say one day they want to wear that uniform," Musk says.
"Get them fired up about, 'yeah I want to be an astronaut, I want to work on aerospace engineering, I want to advance space flight'.
"What today is about is reigniting the dream of space," Musk emphasises. He adds that everyone, all over the world, should be "excited that this is a thing that is made by humans for humans".
Bridenstine adds: "If we can get Tom Cruise to inspire an elementary kid to join the Navy and be a pilot, why cant we get Tom Cruise to inspire the next Elon Musk?"
He says "we need a new generation of many Elon Musks and that's what this launch is about today".
'Done everything to make sure dad's coming back'
Musk says the upcoming launch is "the result of thousands of tests, thousands of design hours and a tremendous number of smart people working incredibly hard to make this day happen".
When asked about the responsibility he feels towards the astronatus, Musk says he felt it "most strongly when I saw their family just before coming here".
"I said we've done everything we can to make sure your dad's coming back."
'This is a dream come true'
"We've had challenges, we've had setbacks, catastrohpic losses of capsules...but that's what's unique about SpaceX," Nasa administrator Jim Bridenstine says, adding that the private company can do things Nasa historically hasn't been able to do.
Elon Musk interjects momentarily to note that the setbacks have all been in uncrewed tests, on the ground.
"They test, they fail, they fix, they fly...until the point where we are today," Bridenstine says.
Musk says: "This is a dream come true."
He added: "When starting SpaceX in 2002, I really did not think this day would occur. I expected 90% chance we'd fail to get to low-Earth orbit with a small rocket.
"So if somebody told me in 2002 I'd be standing here with the Nasa administrator, meeting the astronauts and that we had a rocket and spacecraft on Pad 39A... I'd have thought, man I don't know what you're smoking, but - no way is that true."
How's the weather?
The crew is still monitoring the weather, but so far the launch is still on. Stormy clouds and fog have surrounded the centre since this morning.
More snapshots from inside Dragon
The crew just finished a number of communications checks with the launch director and teams on the ground, and the astronauts are all buckled in now.
Launching amid a pandemic
In the past, such launches saw hundreds of thousands of Americans turn up to the Florida space centre to watch liftoff.
But this year, Covid-19 precautions mean things will look very different.
Only a limited number of staff and officials will be attending the launch, and visitors have been discouraged by Nasa and SpaceX.
The Kennedy Space Center remains closed to the public today, but is due to open to limited numbers on Thursday.
Nasa administrator Jim Bridenstine has asked members of the public to watch the launch online or on television instead, and the agency has publicised its various social media platforms where people can engage with the event.
But Brevard County Sheriff Wayne Ivey on Friday encouraged residents to watch the launch, telling reporters: “If Nasa is telling people to not come here and watch the launch, that’s on them. I’m telling people what I believe as an American.”
Local media say there are already some crowds forming in nearby parks and restaurants to watch the historic launch.
Test your own piloting skills
Earlier this month, SpaceX released an online simulator that lets anyone try their hand at piloting the Dragon 2 craft and docking with the space station.
While we wait for this afternoon's launch, you can have a go at steering the craft with its many controls on the SpaceX site, here.
Astronauts enter the capsule
Hurley and Behnken are inside the Dragon capsule - a few minutes ahead of schedule. Technicians are now strapping them in and checking suits.
They'll also again check two-way communications systems between the astronauts and crew.
Signing the white room wall
Next step: ingress. That's the term for when they climb into the Dragon craft.
As they enter the white room, a sealed off, clean space at the end of the crew access arm that's the last place the astronauts see on earth, they've started a new tradition: signing the wall of the white room.
Going up
Hurley and Behnken are heading up via a quick elevator ride to Level 255 - 255ft (77m) up. From there, they'll walk upstairs to level 265, where the crew access area awaits.
At the pad
The gull-winged Teslas have pulled up at the pad. Hurley and Behnken will now take the lift up the service tower to get into their capsule.
In convoy
The astronauts are in their Tesla motors and are driving down to Launch Complex 39A. Waiting is their Falcon-9 rocket and Crew Dragon capsule.
The famous walk-out
We haven't seen this for nine years - not since the last shuttle mission. Doug Hurley and Bob Behnken walk out to the vehicles that will drive them down to the pad. A last (virtual) hug with the kids.
How we got to this point
Paul Rincon
Science editor, BBC News website
Why is SpaceX launching astronauts to the International Space Station for Nasa?
It all goes back to a tragic accident: the loss of the space shuttle Columbia in 2003. That triggered a dramatic shift in direction for America's human spaceflight programme.
President George W Bush decided to retire the shuttle and build a new space vehicle capable of reaching the Moon.
This opened up commercial opportunities for the routine transportation of cargo and astronauts to low-Earth orbit.
Read about the history of the Commercial Crew Program here.