- Seth Green, best known for his roles in Buffy the Vampire Slayer, Family Guy and the Austin Powers movies will provide the voice for the character known as Joker.
- Keith David, who broke into acting with Disco Godfather and has provided voices for numerous acclaimed videogames including Fallout, Planescape: Torment, Halo 2 and Halo 3, will be voicing Captain David Anderson.
- Lance Henriksen, famous for playing quiet and/or psychotic supporting characters as well as being torn in half by the Alien Queen, takes on the role of Admiral Steven Hackett.
- Marina Sirtis of Star Trek: The Next Generation fame will provide the voice for The Matriach.
The first part of a planned trilogy, Mass Effect is set in 2183 and puts the player in the role of a human soldier exploring the cold darkness of space. Currently an Xbox 360 exclusive, neither Microsoft nor BioWare will comment on rumors of a possible PC release. Mass Effect is scheduled to ship on November 20.