In the series premiere, 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 a surprise admission. Carmela and Irina (Tony's mistress) both suffer as Tony's libido takes a nosedive.