Most performed as a voice actor on several Saturday morning cartoon series. Among these roles were: Ralph Malph on Fonz and the Happy Days Gang (1980); Eric the Cavalier in Dungeons & Dragons (1983); and Stiles on Teen Wolf (1986-1989).

Film credits include EDtv (1999) and Planting Melvin (2005). He also made guest appearances on many TV shows, including CHiPs, The Love Boat, Sliders, and Star Trek: Voyager. He is sometimes credited as "Donny Most".

Most makes a brief appearance 3 minutes into the 17th episode of the fifth season of Family Guy titled "It Takes a Village Idiot, and I Married One".

Most is married to actress Morgan Hart. Most attended, but never graduated from Lehigh University. He has two daughters and lives near Los Angeles, California.