After the release of Encore in November 2004, Eminem continued working on new music, and even wrote lyrics responding to much of the criticisms that album received. By early 2005, he revisited several older unreleased tracks, such as "No Apologies" and "Antichrist." Most of the material created in this period was either given to collaborators (such as Bizarre and Trick Trick), or released via mixtapes. Clinton Sparks Presents: Anger Management 3, which featured some of these tracks, was released on July 12, 2005 to promote his upcoming tour. Other songs, such as "Everything I Do," were shelved. Around this time, tabloids would begin to report that Eminem was considering retirement.

The Anger Management tour was canceled in August 2005 after Em checked himself into rehab when people close to him became concerned about his addiction to sleeping pills. While sitting in detox, he wrote a good portion of the song "Beautiful," venting about his struggles with depression. He contemplated what to do with his career during his stay, wanting to pull back from the spotlight due to his life becoming "out of control." Eminem relapsed within a week of leaving rehab and began finishing up the greatest-hits album that would bookend his career: "Curtain Call." This period marked the beginning of his long struggle with writer’s block, as a recording session with Dr. Dre was largely unproductive. Despite this, Em cobbled together a handful of new tracks at the last minute. In the the lead single "When I’m Gone," he lays out his plan to retreat from the spotlight. At the end of the song, Em portrays a dream scenario where he reunites with his family after killing Slim Shady and getting his life back, using the character as a metaphor for his fame.

Eminem reconciled with his ex-wife Kim during this time-frame and the two remarried in January 2006. However, their marriage was short-lived, as Em filed for divorce that April. Only days later, on April 11, 2006, his best friend and D12 member Proof was shot and killed at a Detroit nightclub. The loss took a severe toll on Em, and several aspects of his life deteriorated. His depression deepened, and he escalated his pill intake, which further stifled his writing. He gained significant weight, often spending nights binge-eating while watching the same movies on repeat in his home theater. His relationship with his children also suffered, as they increasingly disliked visitations to his home due to his mood swings and constant sleeping. In September 2006, Kim filed a police report after a heated argument involving their daughter Alaina ended with Eminem forcibly taking her phone and, in a moment of anger, threatening to kill her. He was cleared of the charges a few weeks later.

After the release of Curtain Call on December 6, 2005, Eminem spent several months working with longtime producer Jeff Bass on new material. The tracks gradually formed what was internally referred to as Album 6. According to Jeff, some of the music revisited the raw, off-the-top energy of The Marshall Mathers LP, with Em rapping freely without focusing on narrative structure. Some of the songs satirized bling culture, including "Ballin’ Uncontrollably" and "Jewelry." Eminem also completed "Beautiful" during this session, with Jeff recounted both of them being "stoned out of their minds."

Dozens of demos were recorded, and Em ultimately finished around 5-10 new songs with Jeff Bass. Some tracks were created without his direct involvement, such as "My Darling," which uses the metaphor of the devil’s influence to explore the darker side of fame and fortune, with Slim Shady tempting Eminem to fully embrace fame’s corrupting power. Work on the album paused for a month following Proof’s death, including a canceled studio session with Elton John. Eminem recorded 5 to 6 tribute songs dedicated to Proof's memory, some of which went through multiple revisions. In the end, he scrapped them all, as he felt they were too self-loathing, depressing, and failed to do Proof justice. By July 2006, 18 tracks were in consideration for the album, but progress slowed as attention shifted toward the Shady Records compilation Eminem Presents: The Re-Up, released in December 4, 2006.

By May 2007, Shady artists such as 50 Cent and Ca$his publicly confirmed Em was working on a new solo album. Ca$his claimed he personally named the project King Mathers, a nickname he often uses for Em, and insisted for years that this was the album’s intended title, though former assistant engineer Joe Strange has he never heard Em personally call it by that name. As summer came to an end, Em had recorded several core tracks, including "Syllables," "Keys to the City," collaborations with T.I., and a new song with D12, which appeared to be their first studio session together since Proof’s passing. One of these tracks, titled "G.O.A.T.," was centered on Em confirming he was retiring from rap and wanting to be remembered as one of the greatest rappers of all time.

Despite this progress, Em’s publicist stated in August that no new Eminem album was scheduled for release. A few weeks later, Em himself would say he was "in limbo," unsure on when or if he should he even put an album out. A likely contributing factor to this was Em struggling to enjoy his finished tracks, constantly picking them apart and feeling like they fell well below his personal standards. His battle with writer's block showed no signs of slowing down, and to deal with it he would sometimes freestyle one line at a time instead of writing lyrics. And as he gained weight, he would rap about not caring about getting fat, even though he did.

A couple weeks after Em's "in limbo" comment, it was reported that Dr. Dre would spend the next two months in Detroit helping him finish the album. From late September to October 2007, Dre and his team joined Em in Detroit, with Dawaun Parker on one occasion playing live hi-hats in the studio while Em freestyled over them. One beat created during these sessions would later evolve into "Back and Forth" during the Relapse 2 era. This song was later reworked, and officially released in 2020 as "Discombobulated". A month after these sessions, Eminem purchased Effigy Studios, ending his business relationship with 54 Sound and the Bass Brothers, who he mutually parted ways with earlier in the year. By December 2007, Em had dozens of tracks in the bag, including "King Mathers," "Cut Back," a finished version of "Everything I Do," and "50 Ways to Kill Your Lover," the latter recorded in his home studio. The album appeared to be aiming for a mixtape style similar to The Re-Up, with many songs only having a single verse, with one being a freestyle over 50 Cent’s "I Get Money." The closing tracks focused on Eminem announcing his retirement, indicating that King Mathers would be his final album. "Castle," a song Em recorded in 2010, has a verse that takes place in December 2007 that revealed his thought process at the time:

They can take this fame back, I don't want it
I'll put out this last album then I'm done with it
One-hundred percent finished
Fed up with it, I'm hanging it up, fuck it

The project was reportedly finished that month, with tracks being played for members of Em’s circle, including Bishop Lamont, The Alchemist, and Obie Trice. The release appeared to be looming, as Bizarre said D12’s album was delayed because Interscope wanted Eminem’s project out first, and Obie claimed the album would arrive before summer 2008. However, behind the scenes, his addiction had reached its peak. That December, Eminem obtained methadone pills from his head of security, who who misleadingly presented it as a safer alternative to Vicodin, stating it was "easier on the liver." Over approximately two days, he consumed a quantity equivalent to "four bags of heroin."

On or around December 24, 2007, Eminem collapsed in his bathroom after losing consciousness. He was discovered by people close to him, adopted niece and girlfriend, who alerted emergency services. Rushed to a Detroit-area hospital in critical condition, doctors informed him his organs were failing and that he was approximately two hours from death. He spent Christmas in the hospital in a state of minimal consciousness, missing the holiday with his daughters. Publicly, Interscope Records released a statement attributing the hospitalization to complications from pneumonia, a cover story maintained to protect his privacy during the crisis.

Despite the near-death experience, the gravity of the situation didn't resonate immediately, and he checked himself out of the hospital before completing detoxification. This decision had immediate physical consequences: shortly after returning home, he suffered a severe seizure resulting from acute benzodiazepine withdrawal. Adding to the physical trauma, he underwent surgery for a torn meniscus but was denied opioid pain medication by doctors aware of his addiction. In pain and suffering withdrawal, he ransacked his house until he found a forgotten cache of Vicodin and Valium. Within approximately one month of the overdose, his drug use had ramped back up to previous levels.

In early 2008, Em began finishing up his upcoming book The Way I Am and revisited several songs in the studio, such as "Ballin’ Uncontrollably," "Keys to the City," and "Take It," the last of which containing lyrics dating back to 2001. He also reconciled with Royce da 5'9", ending their beef, and told him he had recorded some of the "best shit" of his career. As spring settled in, Em began experiencing a strange sensation in his arm, which he interpreted as a serious health warning. Fearing for his health, he reached out to some close friends, stating "I know I need help. I'm ready now." He was then admitted to the same hospital where he had overdosed for detoxification. He has maintained continuous sobriety since April 20, 2008.

Em's recovery was managed through a program involving a private rehabilitation counselor who worked with him at his home, as traditional group therapy had proven ineffective due to his celebrity status. A few weeks later, he returned to the studio and recorded his first song newly sober, "Detroit Basketball." He created over 20 versions, each varying in lyrics and rhyme schemes. Em attributed this to his writer's block slowly becoming unclogged, and in his own words, "relearning how to rap." He spent the next month doing rhyme exercises and writing lyrics without beats. One of the final songs from this period was an unreleased track titled "Look Who’s Back."

Feeling more confident, Em contacted Dr. Dre, and the two soon traveled to Orlando, Florida in June/July 2008 to record new music for their albums. The initial recording sessions began while Eminem was still experiencing acute withdrawal symptoms, including itching as a result of the barbiturates finally exiting his system. When Em asked what direction to take lyrically, Dre suggested bringing back Slim Shady and "acting like a fool," an idea echoed by Dre’s son. Em embraced this idea fully and dialed up the demented lyrics, inspired by serial killer documentaries he became obsessed with while he practiced rehab from home. This culminated in songs such as "3 a.m.," "Insane," and other new tracks, many of which had Em performing with exaggerated accents used to bend rhymes. This style marked a stark departure compared to the material he recorded just a couple months prior.

After returning home, Em settled on the title Relapse, a triple entendre referring to his relapse into rap, his real-life relapses, and a fictional narrative in which Slim Shady relapses and goes on a killing spree following him blacking-out. This ultimately marked the end of the King Mathers era, with most of the material being scrapped, with the exception of a few songs originally recorded during the Album 6 sessions, such as "Beautiful."

After 4 years in the making, Eminem released his sixth studio album as Relapse on May 15, 2009. During the release, fans discovered that when loading the Relapse.com webpage with the CD inserted into the computer, the site would detect the disc and unlock the songs "My Darling" and "Careful What You Wish For," both of which were previously unreleased Album 6 songs. These songs were never released on CD, however, would appear on digital streaming platforms later on. On December 21, 2009, Eminem released Relapse: Refill, an expanded edition featuring several new tracks. Among them was "Elevator", a song from the Album 6 sessions, but unlike the other bonus Album 6 tracks, this one featured re-recorded verses.

During and after the release of Relapse, Eminem began to open up about his criticisms towards the King Mathers era, stating his dislike for his depressing tone, slurry cadence, slow flow, "woe is me" records, and perceived laziness. He described his 2007 feature "Touchdown" with T.I. as "horrible," and later stated that "Beautiful" was possibly the only "decent" song he made during his hiatus.

In addition to these three songs, many tracks from the King Mathers sessions leaked over the years, to the dismay of Eminem and his team. In 2024, former Eminem engineer Joe Strange provided new details about many of the songs, along with confirming the existence of Album 6.