In 2000, Murciano appeared in the film Traffic. In 2001, he starred as Francesco Torres on the short-lived MTV soap opera Spyder Games. That same year, he appeared in Black Hawk Down. It was there that he met Jerry Bruckheimer, leading to him being offered a starring role as Danny Taylor in the CBS mystery drama Without a Trace. The series centered around a missing persons unit of the FBI in New York City. The show ran for seven seasons from September 26, 2002 to May 19, 2009. This role earned him two nominations from the ALMA Award in 2008 and in 2009.