After making his film debut in a small role in "Rocky II" (1979), McCrane became an overnight star in "Fame". His believably touching portrayal of an insecure son of a famous movie star helped to anchor that film. Four years later, the actor tackled another role as a homosexual, this time as brother to Jodie Foster in the uneven "The Hotel New Hampshire". His feature presence declined as he worked more in TV, but, with his receding hairline, McCrane reinvented himself as a character player in such films as "Robocop" (1987), and with his turn as a deputy in the 1988 remake of "The Blob", scripted by Frank Darabont. Following a six year absence, he returned to films as a prison guard in Darabont's "The Shawshank Redemption" (1994).

After spending much of the 80s onstage, McCrane turned to the small screen with a recurring role in a story arc dealing with the recording industry of CBS' "Wiseguy" in 1989. He debuted as a series regular on Steven Bochco's short-lived experimental musical police drama "Cop Rock" (ABC, 1990) before garnering kudos as Cecilia Peck's suitor in the TNT movie "The Portrait" (1993) and as a high-strung detective in the critically-praised "Under Suspicion" (CBS, 1994-95). Switching gears, McCrane displayed his comedic abilities as the twice-divorced heart surgeon in the short-lived ABC sitcom "Champs" (1996). In a memorable 1997 episode of "The X-Files", he was cast as the titular "Leonard Betts", a man capable of regenerating his body. Later that year, McCrane joined the cast of the hit NBC medical drama "ER", playing the gifted but egotistical surgeon Dr. Romano. He could simultaneously be seen as astronaut Pete Conrad in the HBO series "From the Earth to the Moon" (1998).