When Pompeo is only 4, her mother, Kathleen, dies. The grief that her family, including five older siblings, experiences is her first childhood memory in the working-class Boston suburb of Everett, Mass. "Everyone in the house was very upset, and there was me, just knowing there was something terribly wrong," she tells Allure in 2006. "I think having my mother die at such a very young age – when she was 33 – I appreciate life so much."
After meeting boyfriend, fashion photographer Andrew Rosenthal, and serving cocktails in Miami for more than two years, Pompeo moves to New York City, where she is discovered by a casting director. "Where I come from, you don't just say, 'Oh, I'm going to become an actor,'" Pompeo tells PEOPLE. "Talk like that and they think you're crazy." She quickly lands her first gig in a L'Oreal commercial, quits bartending, and makes her TV acting debut on NBC's Law & Order.
After years of making guest appearances on TV series and mediocre indie films, Pompeo makes a memorable turn as Jake Gyllenhaal's sympathetic love interest in the drama Moonlight Mile (right). That same year, she portrays Leonardo DiCaprio's lover in Steven Spielberg's Catch Me If You Can.
Pompeo appears with Luke Wilson (left) and Vince Vaughn in the wildly successful comedy, Old School. Although she's cast as Ben Affleck's secretary in Daredevil and Jim Carrey's girlfriend in Eternal Sunshine of the Spotless Mind, most, if not all, of her scenes are left on the cutting room floor. "I got completely cut out of [Eternal Sunshine] but got so much affirmation to be hired," she tells Allure.
Pompeo is cast as Meredith Grey on ABC's new drama Grey's Anatomy with Patrick Dempsey (right), Katherine Heigl and Sandra Oh. "In the first scene, I have sex with a boy. Then I get into the power position and throw him out," she tells New York's Daily News. "And then I get to perform surgery." The mid-season replacement, which centers around a group of surgical interns juggling love and medicine, cracks TV's top ten, eventually beating CSI for the No. 1 drama spot.
The goings-on of TV's hottest medical drama becomes water cooler talk around America. The pairing of Pompeo's angsty Meredith Grey and Dempsey's Dr. Derek "McDreamy" Shepherd even lands them in ads for fashion retailer New York & Company. "It's awkward with Patrick because he's like my brother," Pompeo tells Entertainment Weekly of her sex scenes with Dempsey. "As soon as the camera is off, I'm like, 'Is your hand on my butt?' But there are millions of girls who have been waiting for this, so I feel an obligation to the fans."
Pompeo's boyfriend of two-plus years, music producer Chris Ivery, 37, presents her with a 3.5-carat diamond ring on her 37th birthday. But it isn't a birthday gift; it's a proposal, which she accepts. "We were six degrees our whole lives, so I feel like we were sort of meant to be," Pompeo tells PEOPLE. "We'll get married eventually, secretly." Pompeo holds to that promise in November 2007, when she quietly weds Ivery in Manhattan's City Hall.
After Isaiah Washington calls costar T.R. Knight an anti-gay slur, the cast is under scrutiny. Despite the controversy, Pompeo nabs a Golden Globe nod and wins a SAG Award for Outstanding Performance by an Ensemble (right, with Heigl and Oh). When Washington is let go, Pompeo tells Ryan Seacrest, "You just have to roll with the punches."
After the writer's strike ends, Pompeo & Co. return with fresh episodes. Appearing on the cover of EW, the Grey's star reveals that after many bumps in the road (including angering devoted fans) the show will leave the "dark and twisty" stuff, inject some signature humor and reunite Mer-Der! "It's nice to see all these relationships moving forward," Dempsey says. "And the characters are making fun of themselves in a good way." Adds Pompeo: "Chemistry wins above everything else. When you have chemistry with someone, you can't stay away from them, no matter how dysfunctional the relationship is."
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