The Game made headlines last month when he dropped "Uncle Otis," a lyrical call-out session on which the Cali rapper poked fun at everyone from Jay-Z to Big Sean to Kreayshawn and 50 Cent. When it comes to hip-hop disses, Game isn't gun-shy, but there is one MC he would never throw shots at.

"One thing that stuck with me is that Eminem is not to be f---ed with ever in hip-hop, ever," he told Sway on Wednesday's "RapFix Live."

Though the pair once collaborated on "We Ain't," a track off of Game's 2005 debut The Documentary, the Compton rapper's famous feud with Eminem cohort 50 Cent has affected his and Slim Shady's relationship. Though Game and Marshall no longer speak, Game holds a great amount of respect for the Detroit wordsmith. "If you notice out of everybody I take a shot at, that's the only person that's untouched. He's in a bubble and you don't even say nothing to Eminem. To anybody that ever does, God bless you," Game said. "He'll end your career."

Game, who is signed to Dr. Dre's Aftermath records, got his start in 50's G-Unit group, appearing on their mixtapes and collaborating with Fif himself. In 2005, a rift grew between the Game and 50, and subsequent shots were fired as the two rappers' camps butted heads outside of New York City's Hot 97 radio station. The two tried to patch things up during a press conference in New York City a few months later, but the truce didn't last. Game even told MTV News that Michael Jackson once tried to bring the two warring rappers together, but things didn't pan out.

The feud between Game and 50 affected both of their relationships with Dr. Dre, who has overseen both careers, and affected Game's relationship with Eminem. "It just had to happen, man, and I was put into a situation where I had to defend myself lyrically and I did," Game said of the many dis records he threw G-Unit's way. "It wasn't personal to anybody; I told that to Dre, I've told that to Paul Rosenberg, who manages Em, and the only the person I hadn't spoke to about it was Em and 50."

"Sometimes stuff happens and I wish it had longevity," he said of the Dre/50/Eminem relationship. "But it didn't, so no regrets on my behalf."