Monaghan's first notable, though minor parts were in episodes of Young Americans (in which she appeared twice), and Law & Order: Special Victims Unit, both in 2001. She made her big screen debut that year in the small role of "Henrietta" in the movie Perfume. This was followed by another small role in Unfaithful in 2002.
Monaghan had a big break in 2002 when she co-starred in the television series Boston Public in the role of Kimberly Woods. After guest-starring for a season, she returned to the silver screen, appeared in It Runs in the Family in 2003, Winter Solstice in 2004, and Kiss Kiss Bang Bang in 2005. Her scenes in Constantine and Syriana do not appear in the final films. However, her audition tape from Constantine earned her an audition for Mission Impossible III and within 20 minutes she had the role of Julia, opposite Tom Cruise.
In 2007, she starred in the remake of The Heartbreak Kid, opposite Ben Stiller, as Miranda, the role originally played by Cybill Shepherd. She also starred in Gone Baby Gone receiving excellent notices for her performance as the female protagonist, Angie Gennaro, opposite Casey Affleck. In 2008, she appeared as "Hannah" alongside Patrick Dempsey in Made of Honor, and co-starred in Eagle Eye with Shia LaBeouf. She also starred in the movie Trucker as Diane Ford.
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