In summer 2005, Mathers embarked on his first U.S. concert run in three years, the Anger Management 3 Tour, featuring Lil' Jon, 50 Cent and G-Unit, D12, Obie Trice, The Alchemist, and others. In August 2005, Mathers cancelled the European leg of the tour and subsequently announced that he had entered drug rehabilitation for treatment for a "dependency on sleep medication".
On December 5, 2006, Eminem released an album compilation entitled Eminem Presents the Re-Up. It started out as a mixtape but Eminem found that the material was better than expected and released it as a full album. It was meant to help launch new Shady Records artists Stat Quo, Cashis, and Bobby Creekwater.
Eminem called into New York radio station Hot 97 during a 50 Cent interview and confirmed he is hard at work on his first studio album in three years. He said, "I'm always working -- I'm always in the studio. It feels good right now, the energy of the label. For a while, I didn't want to go back to the studio ... I went through some personal things. I'm coming out of those personal things [and] it feels good." And though he jokingly said he'd release the new CD "tomorrow", there is no official release date, according to Interscope. Dr. Dre told the Los Angeles Times that he will now devote two months to work on Eminem's new highly-anticipated album, saying "We'll be trying to get his thing done and work on a few things on my own project". On November 13, 2007, Live from New York City the 2005 Madison Square Garden concert that originally aired on the Showtime network in December 2005, was released on DVD. The concert was shown on a few occasions on MTV in Europe. It features D12, Obie Trice and Stat Quo.
It has been reported by TMZ.com that Eminem was reportedly hospitalized over the holidays after suffering from a serious heart condition and severe pneumonia. It was also reported that his weight has ballooned to 212 lbs. He has since been released and is doing well recovering at home. However, rapper Sha Money XL, who said he has "strong ties with the Shady family", has told WENN that he just had influenza and that the reports about his bad health are false. Rapper Trick-Trick, has also said that, "Em just picked up some weight, that's it. He's nowhere (near) 250 pounds or anything like that".
It was announced by NME that Eminem will be releasing an autobiography, The Way I Am, on October 16, 2008. However, Eminem's publicist, Dennis Dennehy, said in a statement, "While there is a book in the works from Eminem in which he details certain aspects of his personal and professional life, the book is still in the process of being written and edited. There is no firm release date scheduled, although it is anticipated to arrive in the latter part of this year."
In 2001, Mathers brought his rap group, D12, to the popular music scene. In 2001, D12 released their hit debut album Devil's Night. The first single released off of the album was "Purple Pills", an ode to recreational drug use. (In the UK this was preceded by "Shit on You", included on the special edition version of the album.) The version of "Purple Pills" released for radio and music television was heavily rewritten to remove many of the song's obscene lyrics, and renamed "Purple Hills". While the first single was a hit, the album's second single, "Fight Music", was not as successful, in part due to its timing in relation to the 9/11 attacks. After their début, D12 took a three-year break from the studio, later regrouping to release their second album, D12 World, in 2004, which featured the popular hit single release "My Band". The other members of D12 have also appeared as guests on all of Mathers' albums since The Marshall Mathers LP.
In April 2006 D12 member Deshaun "Proof" was killed in club brawl involving U.S. military veteran Keith Bender Jr, who was killed by Proof. The eruption is suspected to have been due to an argument over a game of pool. Proof was then allegedly shot by the bouncer Mario Etheridge, Bender's cousin. He was then taken by private vehicle to St. John Health's Conner Creek Campus, an outpatient emergency treatment site, and was pronounced dead on arrival shortly thereafter.
During an interview, D12 member Bizarre said that Interscope doesn't want D12's third album to be released until after Eminem's next album. He also said that Eminem isn't featured on his new album Blue Cheese & Coney Island because "he's busy doing his thing".
Although he typically collaborates with his affiliates (Dr. Dre, 50 Cent, D12), Eminem has collaborated with many other artists including Busta Rhymes (I'll Hurt You, Touch It Remix), Redman (Off The Wall), Kid Rock (Fuck Off), DMX (Go To Sleep), Missy Elliot (Busa Rhyme), Jay-Z (Renegade), Method Man (What the Beat), Notorious B.I.G. (Dead Wrong), Jadakiss (Welcome To D-Block), Fat Joe (Lean Back Remix), Sticky Fingaz (What If I Was White?), Xzibit (Don't Approach Me, My Name), T.I. (Touchdown), and others. Eminem rapped a verse in a live performance of Busta Rhymes' "Touch It" remix at the 2006 BET Music Awards on June 27, 2006. Eminem was featured on Akon's single "Smack That" which appeared on Akon's album Konvicted. He also appears in the video with a new tattoo of his late friend Proof and a green polo. 50 Cent confirmed that on the new G-Unit album, Lock and Load, there will be a track with Eminem. Lil Wayne stated that he has the craziest song for Eminem on his new album, Tha Carter III, but that he hasn't "sent it over yet".
Mathers is also an active rap producer. 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". Eminem has produced some tracks on the new Trick Trick album, The Villain; he's also featured in "Who Want It".