- Nas inks a joint-label deal with Def Jam and Columbia.
- Detroit producer/MC Jay Dee (James Yancey) dies of complications from lupus (the autoimmune disease) on February 10, 2006.
- D-12's Proof (Deshaun Holton) is shot and killed at CCC Club on East 8 Mile Road on April 10.
- Jay-Z ends his three-year break from active recording and bounces back with Kingdom Come. The album includes a diss track to Cam'ron and Jim Jones.
- Nas' Def Jam debut, Hip-Hop Is Dead, dusts up controversy and debate over its title.
- Inspired by the movie 'American Gangster,' Jay-Z records a concept album by the same name.
- On November 12, Donda West, mother of Kanye West, dies from the complications of surgery.
- KRS-One and Marley Marl put two decades of rivalry behind them and collaborate on an album titled Hip-Hop Lives
- Dipset/Byrd Gang rapper Stack Bundles (born Rayquon Elliott) is shot and killed outside his home in Queens, New York.
