Dennis initially had trouble finding work but began to gain notice when he appeared in Breaking Away (1979) and earned good reviews for his role in The Right Stuff (1983).

Known for his famous grin, Dennis Quaid was a versatile actor, performing in both comedic and dramatic roles. Quaid's acting career seemed to reach its peak in the mid-to-late 1980s, with starring roles in such films as Enemy Mine and Innerspace. He also achieved acclaim for his portrayal of Jerry Lee Lewis in Great Balls of Fire (1989).

Quaid's career seemed to lose steam in late-1980s/early-1990s after he fought and kicked a painful cocaine addiction, but he continued to prove his worth in a variety of films, and seems to be experiencing a resurgence in popularity since the late nineties. Some of Quaid's most recent film credits include Traffic (2000) as a lowlife attorney, Far From Heaven (2002) as a closeted husband, and In Good Company (2004), as an aging advertising executive whose new boss is much younger.

Aside from acting, Quaid is also a musician, and plays with his band the Sharks. He also has a pilot's license.

Quaid is a scratch golfer and, in 2005, was named as the top golfer among the "Hollywood set" by Golf Digest. He lends his name to the annual "Dennis Quaid Charity Weekend" (formerly the "Jiffy Lube/Dennis Quaid Charity Classic") in Austin, Texas. The golf tournament attracts numerous celebrities with the proceeds split between local children's charities. He is a member of Bel-Air Country Club in Beverly Hills and tries to stay at homes on private courses when he is on the road.