Character: Izzie Stevens
Why she left in real life: After taking one break to film a movie and another to be with her newly adopted daughter, Heigl finally decided to leave Grey's for good to spend more time with her family. She has, however, expressed regret with how the situation played out — the writers didn't have a chance to craft an appropriate exit for her.
How she was written off the show: She wasn't. In the episode that turned out to be Izzie's last, she attempts to reunite with Alex and is rejected (Alex tells her he deserves better). With this, she packs her bags and heads for the "wilds" of Tacoma, Washington. Later, Alex reveals that she's sent him divorce papers.
What she's up to now: Heigl is now a bankable movie star. She co-starred with Ashton Kutcher in this summer's critically panned action comedy The Killers. Her next (and hopefully better) movie is the comedy Life as We Know It, due out this October. Then she'll play Stephanie Plum in the long-delayed film adaptation of Janet Evanovich's first mystery novel, One for the Money.
Character: George O'Malley
Why he left in real life: Knight asked to be released from his contract after becoming frustrated with a "breakdown in communication" between him and the powers-that-be over his character George's role on the show. He said he felt so marginalized during the fifth season that he thought George had "expired."
How he was written off the show: After deciding to join the army, George is hit by a bus while trying to save the life of a pedestrian. He's so effed up by the time he reaches Seattle Grace that none of the doctors realize it's him until he traces his nickname, 007, on Meredith's palm with his finger. Despite Derek's best efforts, George doesn't make it through surgery.
What he's up to now: From September to November of last year, Knight starred in a Los Angeles production of the Tony-winning musical Parade. This fall, he's returning to the stage to act opposite Patrick Stewart in the Broadway debut of David Mamet's A Life in the Theater.
Character: Erica Hahn
Why she left in real life: The party line is that Erica's "chemistry" with Callie couldn't sustain further storylines, but skeptics have posited that Smith might have been let go because of ABC's efforts to "de-gay" the show.
How she was written off the show: After Callie and Erica both find that they are perhaps not as heterosexual as they once thought, Erica quickly embraces her full-on lesbian-ness and grows impatient with Callie's ambivalence. Erica is also frustrated when Callie voices support for Izzie's decision to cut Denny's LVAD line. So they split, and Erica leaves her post as Head of Cardiothoracic Surgery.
What she's up to now: Smith has two movies due out this year, Fair Game and A Little Help. Reportedly, she has also been writing a show with David Milch — of NYPD Blue and Deadwood fame.
Considering it's been on for seven seasons now, Grey's hasn’t had much cast fallout. Only a handful of significant characters have walked (or have been gurneyed) out the sliding doors of Seattle Grace for the last time. Here's a list of who they are, why and how they left, and what those actors are doing now that they've hung up their scrubs.
Name: Isaiah Washington
Character: Preston Burke
Why he left in real life: ABC gave Isaiah his walking papers after he used a gay slur in reference to T.R. Knight. Unbelievably, Isaiah uttered the offensive term again during the 2007 Golden Globes. WTF? Isaiah later (preposterously) claimed that Knight should have been fired, and he (even more preposterously) went on to posit that his dismissal was rooted in racism.
How he was written off the show: At the end of Season 3, Burke all but leaves Cristina at the altar after realizing that she has changed her entire life to suit him. Then he flees Seattle and never returns.
What he's up to now: Isaiah's acting career, unsurprisingly, seems to have fizzled. In its stead, Isaiah developed a close rapport with the president of Sierra Leone, Ernest Bai Koroma, and accompanied him to the 63rd United Nations General Assembly. Koroma granted Isaiah full citizenship to Sierra Leone on the basis of the ancestry Isaiah has there.
Character: Addison Montgomery
Why she left in real life: After a shaky start (she came between Mer and Der!), Kate won over the grudging hearts of Grey's fans as Derek's estranged ex-wife, Addison. In what is probably the happiest ending on this list, Kate left Grey's to star in her own Shona Rhimes spin-off, Private Practice.
How she was written off the show: The writers tested the waters for a spin-off with a "backdoor pilot" during the third season, which sees Addison visiting her old friend Naomi in an effort to become preggers. Although the pregnancy doesn't pan out, Naomi succeeds in luring Addison to Los Angeles to join Oceanside Wellness.
What she's up to now: Private Practice starts its fourth season in the fall, and Addison still pops up to Seattle for a crossover episode about once a season. Walsh spent the summer co-starring in an off-Broadway play called Dusk Rings a Bell — which, incidentally, we saw and loved. She also recently filmed the drama Waska alongside Jeremy Piven and Mira Sorvino.