Manetti studied acting in Chicago with the Ted Liss Players. His first television role was as a young detective in Jack Webb's Chase (1973–74). He would go on to play pilot "Bobby Boyle" in Baa Baa Black Sheep (1976–78) with Robert Conrad. He followed this up with a role as a bookie on the short-lived NBC series, The Duke (1979), which also featured Conrad in the title role.
Manetti's signature role on Magnum, P.I. lasted for the entire eight-year run of the series (1980–88). He also had co-starring roles in 25 feature films and guest starred on many other television shows, including Rockford Files, Emergency!, Starsky & Hutch, Tenspeed and Brownshoe, Fantasy Island , Battlestar Galactica, Renegade, Quantum Leap, JAG and Walker, Texas Ranger. He also had a minor role in the 1993 film CIA II: Target Alexa.
Since July 2011, Larry and Nancy Manetti have hosted a weekly radio program on CRN Digital Talk Radio Networks.

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