Tony Soprano, a Capo in the Jersey mafia, begins seeing a therapist because he is stricken by panic attacks. During his session, Dr. Melfi learns of his two conflicted families. Tony is stressed by his unhappy wife, rebellious kids and his demanding mother. On the business side, Tony feels pressure from his willful nephew, while also engaging in a power struggle with his Uncle Junior.

Christopher and Brendan take some initiative in a truck hijacking, but their plan backfires when it angers Uncle Junior. Tony's crew does a favor for A.J.'s science teacher. After one too many accidents, Tony forces Livia to move into a nursing home against her will.

Tony, Paulie and Sylvio enter into a new business deal with a Jewish hotel owner, while Tony struggles with the terminal illness of his long-time friend and current don, Jackie Aprile. Meadow asks Christopher for a favor that could get him in trouble. After consulting Livia, Junior has his triggerman, Mikey Palmice, send Christopher and Brendan a clear message.

When Jackie Aprile loses his battle with cancer, Tony and his crew agree to give Junior what he wants. However, they have ulterior motives. Christopher goes from fear to anger when he discovers Brendan's fate. Tony sends a cop on his payroll to investigate Dr. Melfi, while Carmela gives him an ultimatum about his therapy.

Tony takes Meadow to Maine on a college tour. While there, Tony stumbles across an ex-mobster who went into the witness protection program after ratting out several of Tony's old comrades. Tony and the mobster begin stalking each other while Tony does his best to hide his activities from his daughter. Carmela receives a visit from Father Phil and the two have a close encounter.

Tony's crew is unhappy when Junior refuses to respect old arrangements. Junior shows reckless behavior by taxing long-time members and ordering hits on top earners. Tony brings in Johnny Sack from New York in hopes of tricking Junior into relenting. Carmela is frustrated when she learns that Tony's therapist is a woman. Her anger grows when Tony is rendered impotent by his medication.

After A.J. is suspended from school for drinking sacramental wine, Tony begins remembering his own childhood days when he learned of his father's unique lifestyle. Livia learns of her son's therapy during a visit from A.J.

The Soprano crew begins to do some frantic house-cleaning as rumors of FBI indictments begin to surface. Christopher gets depressed when he isn't named on the list and it results in some poor decisions. Livia tells Junior about Tony's therapy.

Tony and Sylvio plan drastic action when they hear some disturbing news about Meadow's soccer coach. Tony learns of a secret that Junior would rather keep under wraps. Tensions flare when they begin needling each other during a golf game. And this results in Junior giving up a long term relationship.

Tony has a disheartening experience when he tries to strike up new friendships in the civilian world. Christopher and Adriana try their hand in the music recording business, but their plans backfire in their faces.

Tony is shocked to learn that his old friend, Big Pussy, may be a rat. He sends Paulie to investigate when Pussy acts suspiciously. Junior reaches the breaking point when he learns that Tony has been working behind his back. He and Livia begin conspiring to take action against Tony.

Tony is more depressed than ever over Pussy's disappearance. He increases his medication and this causes him to have hallucinations of a beautiful Italian girl living next door. Meanwhile, Junior and Mikey send two hit men after Tony, but all doesn't go according to plan.

Tony begins to retaliate for the attempt on his life, but he is stunned when he learns that his mother and uncle were behind it. Junior tries to escape when he suspects that Tony will come after him, but the Feds intervene before Junior can get away. Livia pits Artie against Tony in a last-ditch effort to save herself. Carmela finally lays down the law with Father Phil.