Grey's Anatomy burst onto screens in 2005, making household names out of stars like Ellen Pompeo and Katherine Heigl.
While the series remains a primetime staple, both actresses have exited the show and moved on to new projects.
As part of Variety's Actors on Actors conversation, the pair reunited to talk about their time on the show, and there were some big reveals.
Grey's Anatomy Season 1 was a midseason replacement for ABC in 2005, and while the sudsy medical drama had huge ratings, the stars were worried the show would never air.
"Those numbers, I don't even know if people can count that high anymore," Pompeo stressed.
"I was nervous that they were not going to air it," Heigl recalled, adding:
"There was a moment where it was unclear if they were going to air it. … It felt like the network or studio somebody didn't quite like what we were doing."
Pompeo went one step further and revealed that an eleventh-hour title change was planned.
If you watch Grey's Anatomy online, you know the series has revolved around Meredith Grey and those in her orbit at the focal hospital since the beginning.
It's hard to imagine the show titled Complications after watching Grey's Anatomy Season 1 Episode 1.
"It was just like somebody had died, and everybody on set felt we'd been working so hard, and we loved the show so much, and if they changed the name, it'll never go, it's a horrible title, and it was just this collective mourning on set," Pompeo said.
"But that only lasted for a day or two."
The pair also delved into Heigl bowing out of the show in 2010 after withdrawing her name from Emmy contention.
"I was up here in my headspace, in my gut, in my mind, in my life. I was just vibrating at way too high of a level of anxiety," the Izzie Stevens star shared.
"For me, it's all a bit of a blur, and it took me years to learn how to deal with that, to master it."
"I can't even say that I've mastered it, but to even know to work on it, that anxiety and fear — and stress is stress," Heigl said, before adding that it took her several years to be "comfortable with my role as a villain."
The star added that she didn't anticipate an adverse reaction to her decision.
"There was no part of me that imagined a bad reaction. I felt really justified in how I felt about it and where I was coming from."
Heigl said that the show gave her a confidence that "was a false sense of confidence."
"It wasn't rooted in anything real. It was rooted in something that couldn't and maybe wouldn't always last for me."
"So then I started getting real mouthy, because I did have a lot to say, and there were certain boundaries and things that I was not OK with being crossed," she recalled.
"If you cannot stand up for yourself in this industry, very few people will stand up for you, so you better learn how to, and you better be OK with them not liking you for it."
"I'd like to see other people try to walk a mile in your shoes during that time, and let's see how they would've handled it," Pompeo said in support of her friend.
Pompeo, who exited Grey's Anatomy as a series regular earlier this year, spoke about why she stayed so long.
She explained to Heigl that the anxiety of having a job or not kept her on the show.
The actress was also frustrated about Meredith's inability to have a relationship that worked.
"Somehow, Meredith can't figure out how to make a relationship work still, after all this time, and I guess if she were to make it work, then where's the conflict? There has to be conflict," Pompeo explained.
"It's not that I don't think there shouldn't be conflict," she added.
"There should be conflict. I guess I just have different ideas of about what the conflict should be."
The good news is that Pompeo doesn't think she has said "a complete goodbye" to the show.
"I will be making some appearances hopefully next year if I can find some time," she shared.
Grey's Anatomy is set to return to ABC in 2024.
Paul Dailly is the Associate Editor for TV Fanatic. Follow him on Twitter.