Ellen Pompeo

An Early Loss

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."

A Bar Discovery

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.

February 21

On the Chopping Block

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.

September 23

America's McSexiest Couple

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."

January

A Cast Under Fire

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."