On April 30, 2005, he defeated John Ruiz by a unanimous decision in a 12-round match for the World Boxing Association (WBA) heavyweight Championship. However, as of May 18, 2005, it was [1] reported that Toney failed his post-fight drug test, testing positive for the anabolic steroid stanozolol. This led to the New York Athletic Commission changing the bout's official outcome to a "no-contest", deducting the win from Toney's career record, and banning him from boxing for 90 days. The WBA ordered that Ruiz be reinstated as its champion and that Toney be ineligible for another WBA Heavyweight title shot for two years. Toney defended himself by claiming that the steroids were given to him by a doctor to treat an injured arm that occurred during his victory over Rydell Booker in his previous fight. Toney was also subject to a civil lawsuit by Ruiz claiming that Toney's illegal use of steroids gave him an edge in the fight.

In his bout after the Ruiz fight, Toney won a unanimous decision victory over former heavyweight contender Dominic Guinn. Toney next fought against Hasim Rahman on March 18, 2006, for the WBC Heavyweight title. The result was a twelve-round majority draw and Toney weighed a career-high 237 lb for his lackluster performance.

Toney's next two outings were split decision and unanimous decision losses on to Samuel Peter. The first fight was held in Los Angeles, California on Sept 2, 2006, and was a controversial decision. The return bout was held in Hollywood, Florida, on January 6, 2007, and Toney once again lost a decision to Peter. Both fights were WBC eliminator bouts for the belt held by Oleg Maskaev.

Toney returned to action in May 2007 and won a ten-round split decision over Danny Batchelder. Following the bout, Toney once again tested positive for boldenone and stanozolol and was fined $2500 and banned from boxing for a year, Toney appealed the suspension and it was reduced to 6 months after he appeared before the CSAC and claimed he didn't knowingly take any steroids and suggested that he was set up and someone had tampered with his water bottle. Many state that Batchelder was the true winner of the match, as Batchelder circled around Toney plastering him with jabs and straight right rands, noticeably hurting him in the 9th round.

On July 16, 2008, Toney's rematch against Hasim Rahman was stopped in the third round. An accidental headbutt by Toney opened a cut above Rahman's left eye. The ring doctor stopped the fight after determining that the cut was blocking Rahman's vision. Initially, the fight was called as a TKO win for Toney, but this was overruled by the California State Athletic Commission and the fight was declared no-contest.

Toney's next bout came on December 13, 2008 against Fres Oquendo. Oquendo was penalized 1 point in round eight for a rabbit punch, which would prove to be the deciding factor in the fight. Toney won a close split decision.

On September 12, 2009, James fought heavyweight fighter Matthew Greer (12-5-0 11KO) at the Pechanga Resort & Casino, looking visibly trimmer than he had been in recent years.[1] James won via TKO victory in round two.

James Toney is the current NABO and IBA Heavyweight champion