Determined to get serious about her career, Ellen Pompeo moved to Los Angeles in 2001 and finally struck gold in 2002 when she was tapped by director Brad Silberling for a crucial role in his film "Moonlight Mile". Despite her thin resume and non-existent name value, Silberling--who also penned the the script--saw in Pompeo the sparkle he needed to make his cast complete. As Jake Gyllenhall's romantic interest in the grueling film about death, grief, and dealing with personal loss, Pompeo provided a desperately needed ray of hope, taking an underwritten part and making it breathe. Despite the film's mixed reviews, critics were generally unanimous regarding Pompeo's performance.

Pompeo's next high-profile project was Steven Spielberg's "Catch Me If You Can" (2002) In it, Pompeo played one of the long string of women that Frank Abagnole (Leonardo DiCaprio) cons, loves, and leaves. On a roll, Pompeo landed a short-but-sweet part in big-screen adaptation based on the Marvel Comics icon "Daredevil" (2002) as Karen Page, the loyal secretary of Daredevil's alter ego, a.k.a. Matt Murdock (Ben Affleck). Unfortunately for Pompeo, the sweet role wound up to be more short than sweet: Finding that the Karen-Matt subplot of unrequited love detracted from the primary romance between Daredevil and Electra (Jennifer Garner), most of Pompeo's scenes were left on the cutting room floor.

Pompeo fared much better in her next role, the lowbrow but very funny campus comedy, "Old School" (2003). Directed by Todd Phillips, Pompeo filled the role of Nicole, the love interest of the central character Mitch (Luke Wilson) and the principal female in a testosterone laden frat house, When "Old School" grossed over $75 million at the box office, Pompeo's bankability shot up as well.

Pompeo also appeared in a string of lower profile projects, including the little-seen thriller "Undermind" (2003) and the poorly conceived Spanish-made action film "Art Heist" (2004) opposite Daniel Baldwin, as well as the comedy short "Nobody's Perfect" (2004), directed, co-written and starring Hank Azaria. She also has a guest stint on an episode of the final season of "Friends" in 2004.

In 2005, after a year of doing nothing but reading scripts looking for the project that suited her best, Pompeo returned to the small screen as Dr. Meredith Grey, the titular lead of the mid-season medical dramedy "Gray's Anatomy" Pompeo headlined a solid ensemble cast that included Patrick Dempsey, Chandra Wilson, and Sandra Oh, and quickly earned TV star status when "Grey's Anatomy" premiered to strong ratings and was immediately granted regular occupancy of the coveted post-"Desperate Housewives" timeslot as a reward.