(written from a Production point of view)
He is probably best known for his first major television role on Newhart as the "First Darryl" (as in, "Hi, I'm Larry, this is my brother Darryl, and this is my other brother Darryl."). However, he had two minor film roles beforehand, first in 1981's Escape from New York, co-starring fellow DS9 guest actor Adrienne Barbeau, and then in 1982's Firefox, with fellow Trek performers Ward Costello and Richard Derr.
Since Newhart ended, he has made guest appearances on various television shows, including Seinfeld (with Jason Alexander and Heidi Swedberg), Murphy Brown (with Brad Blaisdell, Warren Munson, Michael Bailey Smith, and Ken Thorley), Roswell (starring William Sadler), and Providence (with Michelle Krusiec, Richard Riehle, and Concetta Tomei). He also reprised his role as Darryl #1 in two episodes of the hit sitcom Coach, and made a cameo appearance in an episode of Newhart star Bob Newhart's later series, George & Leo. Star Trek: The Original Series guest actor John Fiedler, who was associated with Newhart's previous show, also appeared in the latter episode.
Papenfuss has also played Adolf Hitler (or a parody of him) on several occasions, most recently in the 2002 film How to Kill a Mockingbird.