Among his better known game roles are Nathan Drake in the Uncharted series, Desmond Miles in the Assassin's Creed games, Doctor Edward Richtofen in the Zombies modes of the Treyarch-developed Call of Duty games, Chris Ramsey on Port Charles, Ghost Rider in Marvel: Ultimate Alliance, El Jefe and Le Paradox in Sly Cooper: Thieves in Time, The Penguin in the Batman: Arkham series, General Zod in Injustice: Gods Among Us, Doctor N. Gin in the Radical Entertainment Crash Bandicoot games, the corrupt Personality Cores and Defective Turrets in Portal 2, Merasmus the Magician and the Bombinomicon in Team Fortress 2, numerous heroes in Dota 2 and the ever-popular Deadpool in Hulk Vs. and numerous Marvel Comics video games.
In animation, he is also the voice of the Kraang in the 2012 Teenage Mutant Ninja Turtles cartoon, Raphael in the 2007 TMNT CGI movie, Snow Job in G.I. Joe: Renegades, Cyclops in Wolverine and the X-Men, Superman and his kid clone Superboy in Young Justice, Madara Uchiha on Naruto Shippuden, and Peter Hastings on Pretty Little Liars.
- Miner (Rebellion)
- Vehicon #1 (Legacy/Inside Job)
- Vehicon #2 (Synthesis)
- He is married to his Port Charles co-star Jill Murray, and has two children.
- He has written a book about the cinematic production of Uncharted 3 titled "Uncharted: Drake's Journal".