After retiring from the NFL, Mayhew attended Georgetown University Law Center. He graduated in 2000 with a J.D. degree. Mayhew initially was the Senior Vice President and later promoted to acting General Manager of the Detroit Lions after the firing of Matt Millen. On December 29, 2008 it was announced that Mayhew would be officially promoted to General Manager. Mayhew's first move as acting General Manager was the trade of wide receiver Roy Williams and a 7th round draft choice to the Dallas Cowboys for Dallas' 1st, 3rd and 6th round draft choices in the 2009 NFL draft. In the 2011 NFL Season, Mayhew's Detroit Lions made the playoffs for the first time since 1999.