Epstein won the Academy Award for Best Documentary Feature twice for the films The Times of Harvey Milk (1984) and Common Threads: Stories from the Quilt (1989).

He also directed the documentaries Word Is Out: Stories of Some of Our Lives (1977), The AIDS Show (1986), The Celluloid Closet (1996), and Paragraph 175 (2000).

He made his narrative directorial film debut with the historical drama Howl (2010) followed by Lovelace (2013).

In 1987, Epstein and his filmmaking partner Jeffrey Friedman founded Telling Pictures, a production company that focused on feature documentaries.

[4] Epstein's works also include scripted narratives such as Howl, his award-winning film about Allen Ginsberg's controversial poem by the same name (starring James Franco), and Lovelace, the story about the life and trials of pornographic superstar Linda Lovelace (starring Amanda Seyfried).