Mathers is also active as a producer of rap records. Besides being the executive producer of D12's two albums, Devil's Night and D12 World, he has also executive produced Obie Trice's Cheers and Second Round's on Me as well as 50 Cent's Get Rich or Die Tryin' and The Massacre. In addition, Mathers has produced and appeared on several songs by other famous rappers, such as Jadakiss' "Welcome To D-Block", Jay-Z's "Renagade" and "Moment of Clarity" Lloyd Banks' "Warrior Part 2", and "Hands Up", Tony Yayo's "Drama Setter", Trick Trick's "Welcome 2 Detroit", and Xzibit's "My Name" and "Don't Approach Me".
Most of The Eminem Show was produced by Mathers himself, with co-production from longtime collaborator Jeff Bass. He also split the production with Dr. Dre on Encore. In 2004, Mathers was the Executive Producer of 2Pac's posthumous album Loyal to the Game with 2Pac's mother Afeni Shakur. He produced the UK #1 single "Ghetto Gospel" which featured Elton John.
On certain tracks on the album, 2Pac's voice was slowed down and digitally altered to match the beat and make him say things like "2005" and "G-Unit", angering many fans. He has also produced "The Cross" off Nas's album God's Son. On August 15, 2006, Obie Trice released Second Round's on Me. Eminem produced 8 tracks on the album. He was also featured in the song "There They Go".