After suffering a series of mysterious anxiety attacks, New Jersey mob boss Tony Soprano agrees to see a psychiatrist, Dr. Jennifer Melfi. As he opens up to the doctor, Tony reveals details about his problems at home and at work that involve his wife Carmela, his kids Meadow and Anthony Jr., his Uncle Junior and his domineering mother Livia.

With acting boss Jackie Aprile dying of cancer, Tony prepares for a power struggle with Uncle Junior. Christopher and his associate Brendan make trouble for themselves when they jack a truck full of DVD players. Tony's mother Livia finally agrees to live in a retirement community. Big Pussy and Paulie Walnuts are sent to find a stolen car.

Uncle Junior's associate Mikey Palmice stirs things up by making Junior think Tony wants to be next in line for boss. Meanwhile, Tony, Paulie and Silvio deal with Hasidic family problems.

Jackie Aprile's health worsens, forcing Tony to make a tough decision. Meanwhile, Anthony Jr. learns the true nature of his father's job in 'waste management.' Also, Tony hires sleazy police lieutenant Vin Makazian to investigate Dr. Melfi's background.

During a trip to Maine for Meadow's college interviews, Tony sees a man he believes is a relocated mob snitch. Back at home, Carmela receives comfort from Father Phil.

At Tony's suggestion, Junior is made acting boss after Jackie dies. In therapy, Tony surprises Dr. Melfi with an admission. Carmela and Irina (Tony's mistress) both suffer as Tony's libido takes a nosedive.

After stealing the 'sacramental wine' from the school chapel, Anthony Jr. is suspended. Tony is concerned that his bad influence is responsible for his son's behavior, and has a series of disturbing flashbacks in which he remembers learning that his own father was in the mob.

At the wedding of Larry Boy's daughter, the 'boys' find out they're going to be indicted, and make a premature exit to get rid of incriminating evidence at home. Upset that he isn't getting the notoriety of other family members, an agitated Christopher has an ugly encounter with a bakery clerk.

Uncle Junior enjoys a romantic tryst in Boca with his girlfriend Bobbi, not realizing that she's been gabbing to her beauty-parlor friends about his oral talents. Meanwhile, controversy arises when Meadow's soccer coach announces he's leaving the school.

Christopher and Adrianna cut a deal with a famous gangsta rapper who claims that Hesh pocketed royalties belonging to a cousin who recorded several hit songs decades ago. Meanwhile, Tony plays golf with Cusamano and his white-bread friends.

After Jimmy and Pussy are arrested in an FBI raid, Makazian tells a stunned Tony that Pussy may be wired for the Feds. Tony sends Paulie to find out for sure. Later, Tony learns that Makazian might be trying to frame Pussy to get out of his gambling debts.

Hit men are sent out to whack Tony, who comes out of his depression when he meets Isabella, an Italian exchange student staying next door.