Pearlman is known for his role as Vincent in the television series Beauty and the Beast; the series won the actor a Golden Globe award. He later went on to star as Deathstroke figure known as Slade in the animated series Teen Titans, Clarence "Clay" Morrow in Sons of Anarchy, the comic book character Hellboy in the films of the same name, and as the narrator of the post-apocalyptic game series, Fallout.
In 2010 he provided the voice of the Stabbington brothers in Tangled, Disney's animated film adaptation of Rapunzel. He is currently the narrator of the television series 1000 Ways to Die on Spike. Perlman is known for playing roles which require make-up, some to the point where his entire body is covered or his face requires full facial prosthetic.
Some examples include his first film role in Quest for Fire, where he played a Neanderthal, The Name of the Rose where he plays a disfigured hunchback, The Island of Dr. Moreau where he plays a half man/half animal, Star Trek: Nemesis in which he is the Reman viceroy and the Hellboy films where he plays the titular demon.