Another original “Grey’s Anatomy” character has flatlined.

Sure, Justin Chambers’ surprise exit from ABC’s long-running medical drama has left fans reeling — but it’s far from the first time they’ve been shocked by a star character’s sudden departure.

Chambers’ Dr. Alex Karev was a staple of the show for 15 years, which premiered in 2005 when the main characters were interns at a Seattle hospital. Now, only Dr. Meredith Grey, played by Ellen Pompeo, 50, remains among the original interns in the series created by Shonda Rhimes.

The 49-year-old actor announced he would be leaving the show to pursue other gigs, though Page Six reports that the actor was also seeking treatment for “stress, depression and life-coaching,” according to one source. “There is a lot going on with [‘Grey’s Anatomy’] behind the scenes right now.”

But this season isn’t the only one with more drama than the confines of Grey Sloan Memorial Hospital. The show has seen an unusually high volume of eyebrow-raising scandals and cast departures, many of which sent shock waves through the world of TV.

After all these years, the mounting losses haven’t done a thing to damage the show’s enduring viewership: “Grey’s Anatomy” is still the third-most watched show on network TV in the coveted 18 to 49 demo.

Here’s a look back on the most high-profile departures in “Grey’s” history — which, should be noted, does not include Pompeo. She’s currently the highest-paid actress on a TV drama and is safely signed on for the show’s upcoming 17th season. But then again, as history proves, no one’s safe in Shondaland.

Katherine Heigl

Heigl, 41, played Izzie Stevens on “Grey’s Anatomy” from 2005 to 2010 (winning an Emmy in 2007) and in her downtime, she became the queen of rom-coms, with movies such as “Knocked Up” (2007), “27 Dresses” (2008) and “The Ugly Truth” (2009). But the year after her Emmy win, she didn’t submit herself because of the quality of the writing — she said she didn’t feel that the material warranted consideration.

After that much-publicized controversial comment, it was over. She reached an agreement with Rhimes to be released from her contract.

Izzie never officially died on the show, but her storylines became increasingly outlandish: getting cancer, getting fired from her job and divorcing Alex (Chambers). Heigl got a rep for being difficult to work with and hasn’t recovered since.

Patrick Dempsey

In one of the biggest shockers, McDreamy himself got the axe. Dempsey, 53, was once one of the faces of the show, starring as Derek “McDreamy” Shepherd for 11 seasons (2005-2015). He was unceremoniously written off via a tragic car crash, leaving fans seriously McBummed.

Although he and Rhimes both publicly stated they were cordial and that he wanted to leave, co-star Ellen Pompeo later appeared on “Red Table Talk” where she said, “We haven’t spoken since he’s left the show.”

“I think after a certain period of time, no matter how much money you make, you want control out of your own schedule,” he told People about his departure in 2015.

Sara Ramirez

Ramirez, 44, who played Dr. Callie Torres for 11 seasons, reportedly surprised Rhimes herself when she announced her departure from the show in 2016. Rhimes told Vulture that this departure was different from all the others. Speaking at Vulture Festival that year, Rhimes said, “It wasn’t a big, planned thing. I had a different plan going and then Sara came and said, ‘I really need to take a break.’ “ She left after Season 12. Rather than dying, Callie was written off by her moving to New York.

Isaiah Washington

In October 2006, backstage rumors surfaced that Washington, 56, who played surgeon Preston Burke, reportedly used a homophobic slur to refer to his co-star T.R. Knight in an argument with Dempsey. Knight came out publicly as gay following the incident, and Washington issued an apology. Fast forward to the Golden Globes in January 2007, where “Grey’s” was named Best Drama.

On June 7, 2007, ABC announced it had decided not to renew Washington’s contract, and that he would be dropped from the show — though he did return for an episode in 2014. That one, coincidentally, marked the departure of yet another high profile actor on the show, Sandra Oh, 48. As far as anyone knows, Oh left to pursue other opportunities. In 2019, she won a “Best Actress” Golden Globe for her performance in the smash hit “Killing Eve.”

T.R. Knight

Knight, 46, was cast as Dr. George O’Malley and appeared in Episode 1. O’Malley worked his way up from intern to resident, having a major love storyline with Izzie (Heigl). In 2009, two years after Isaiah Washington left the show after his comments regarding Knight, “Grey’s” wrote Knight’s character out of the show.

The departure was slow and painful. Knight said he watched his character gradually get less airtime. By that point, he and Rhimes were experiencing what he called a “breakdown in communication.” He was surprisingly candid in explaining why he asked to leave the show.

“My five-year experience proved to me that I could not trust any answer that was given [about O’Malley],” he told Entertainment Weekly. “And with respect, I’m going to leave it at that.”

Brooke Smith

Smith, 52, was brought on the show in 2006 to play the workaholic attending surgeon — who happened to be a lesbian. The character, Dr. Erica Hahn, sparked up a romance with Callie (Ramirez), leading up to a passionate (network TV!) kiss. She was booted from the show in 2008, reportedly in an effort to tone down the LGBTQ storylines on the show, according to E!

Rhimes denied that Smith’s sexuality was her reason for leaving the show — certainly “Grey’s Anatomy” hasn’t shied away from queer characters, she pointed out. Nevertheless, the departure sent the message that it’s “OK to be gay — just not too gay,” said NPR’s TV critic Andrew Wallenstein.

Jessica Capshaw and Sarah Drew

One man’s ceiling would seem to be another man’s floor on “Grey’s Anatomy.” Jessica Capshaw, who had been on the medical drama for 10 seasons as Dr. Arizona Robbins, and Sarah Drew, who played Dr. April Kepner for nine seasons, were written out at the end of Season 14. The timing of the double exit raised eyebrows as it coincided with star Ellen Pompeo signing a new two-year deal that paid her as much as $20 million a year.