Red & Meth starred in a Fox sitcom titled Method & Red, but they later disowned the series due to lack of creative control. In 2001, they starred together in the movie How High. On March 27, 2007 Redman confirmed on BET's Rap City: Tha Bassment that the sequel to How High, How High 2, is being written.

The duo have known each other since they were kids before signing with Def Jam. While at Def Jam they reunited in 1994 on tour and met again in 1995 in the recording studio of Tupac Shakur's "Got My Mind Made Up" for his multi-platinum album All Eyez on Me. After this they had friendly battles freestyling with each other on Yo! MTV Raps which led to their collaboration single How High. In 1999 the two MCs appeared together on "Rap Phenomenon" from The Notorious B.I.G. posthumous album Born Again.

Method Man often gives a shout out to Redman on tracks that do not feature Redman; this usually comes in the form of "What up, Doc!" referring to Redman's alias "Funk Doctor Spock". In 2013 Method Man and Redman previewed a new track called "Lookin’ Fly Too". They continue to record together with both eyeing careers beyond DefJam.