- 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. American Gangster
- 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.
- In the months leading up to the 2008 presidential election, Democratic nominee Barack Obama galvanizes hip-hop artists into action, leading to a slew of Obama rap tributes.
- Jay-Z becomes the first rapper to headline Glastonbury, the largest greenfield music and performing arts festival in the world.
- Brooklyn MC Jamal "Gravy" Woolard is recruited to play the Biggie Smalls in the biopic Notorious.
- Eminem ends his four-year sabbatical with the release of Relapse. The album debuts at No. 1 and scores a Grammy win for Best Rap Album.
- T.I. is sentenced to 12 months in federal prison for illegal weapons possession.
- DJ AM is found dead in his New York apartment, following a series of ominous tweets.
- Four revered MCs Detroit's Royce da 5'9", California's Crooked I, New Jersey's Joe Budden, and Brooklyn's Joel Ortiz join forces to form a supergroup named Slaughterhouse. Their self-titled debut re-energizes the lyricism movement in hip-hop.
- Gang Starr co-founder and hip-hop icon Guru dies on April 19 after a grueling battle with cancer.
- Bun B's third solo album, Trill OG, becomes the first album in five years to receive The Source magazine's 5-mic award.
- Wyclef Jean declares for presidency of his native country Haiti. Jean's candidacy is eventually rejected by the electoral council.
