At the beginning of the sixth season, Tony is shot by the now senile and confused Uncle Junior. Rendered comatose, Tony dreams he is a salesman on a business trip, where he mistakenly exchanges his briefcase and identification with a man named Kevin ...

At the beginning of the sixth season, Tony is shot by the now senile and confused Uncle Junior. Rendered comatose, Tony dreams he is a salesman on a business trip, where he mistakenly exchanges his briefcase and identification with a man named Kevin Finnerty. Tony's recovery from the shooting changes his outlook, and he tries to mend his ways. However, he is faced with more problems in his business life. Vito Spatafore is outed as a homosexual and Tony is urged to deal with the problem by Phil Leotardo, now acting boss of New York with Johnny Sack in prison. When Tony fails to act, Phil intervenes and kills Spatafore. Tony's crime family commits a reprisal murder and once more it appears that the families are on the verge of all-out war.

Tony considers killing several of his associates for relatively minor infractions. Christopher is unable to leave the mob, deflecting his problems by relapsing into drug addiction and killing his old Narcotics Anonymous sponsor. He is then seriously injured in a car accident that he causes while driving under the influence of narcotics. Tony, the sole passenger, is not badly hurt, and suffocates Christopher to death. A.J. is dumped by his fiancée and slips into depression, culminating in a failed suicide attempt in the backyard pool. Dr. Melfi is convinced by friends that Tony is making no progress and may even be using talking therapy for his own sociopathic benefit. She drops him as a patient.

Johnny Sack dies from lung cancer while imprisoned and Leotardo consolidates his position in the Lupertazzi family. He has his opposition for leadership killed and then officially takes over. In a resumption of their past feud Phil will not compromise with Tony on a garbage deal. When Tony assaults a Lupertazzi soldier for harassing Meadow on a date, Phil seizes a chance for revenge. Phil orders the executions of Bobby Baccalieri, who is shot to death, Silvio, who ends up comatose, and Tony, who goes into hiding. A deal is brokered where the rest of the Lupertazzi family agree to ignore the order to kill Tony, and give Tony an opportunity to go after Phil. An FBI agent informs Tony of Phil's location and Tony has him killed. With Phil’s death, the threat from New York is presumably extinguished and Tony, Carmela, Meadow, and A.J. meet for a casual dinner.