Determined to succeed in acting, Pompeo moved to Los Angeles in 2001. A turning point came when she was selected by director Brad Silberling in 2002 for a role in his film Moonlight Mile playing Jake Gyllenhaal's sympathetic love interest. She also appeared in the film Daredevil playing Matt Murdock's (Ben Affleck) secretary Karen Page, but most of her scenes were deleted from the theatrical version of the film. In 2002 and 2003, Pompeo appeared in Catch Me If You Can and Old School. Television guest roles include two episodes of Law & Order and an episode of Friends. She portrayed Jim Carrey's ex-girlfriend, Naomi, in the 2004 film Eternal Sunshine of the Spotless Mind. Although her scenes were cut from the film, she felt grateful that director Michel Gondry chose her to appear in his film.

Pompeo landed her first major role in the ABC medical drama Grey's Anatomy, as the title character, Meredith Grey, a surgical intern at a prestigious hospital. The show became the high