Edie Falco stars as title character Jackie Peyton, a drug addicted emergency room nurse in a New York City hospital. For Jackie, every day is a high wire act of juggling patients, doctors, fellow nurses and her own indiscretions. The second season of the Showtime Original Series NURSE JACKIE continues its look deep inside the complicated heart and soul of a functioning addict, a loving wife, mother, and a first-class nurse.
After the confrontation with Eddie at the end of season one, it’s now a few months later. Jackie has cut ties with Eddie and is determined to dive back in and spend more time with her family. Back at All Saints, she deflects blame about the narcotic shortage and endures Sam, the altered nurse and his newfound sobriety.
Without Jackie's knowledge, Eddie keeps up his friendship with Jackie's husband Kevin. In the meantime, Jackie has to cover for O'Hara who drank a little too much over her grief.
O'Hara offers financial help, but Jackie and Kevin refuse to take it. Eddie and Kevin's secret friendship is revealed.
When a patient is suffering, Jackie supplies the patient with illegal marijuana to ease the pain. Meanwhile, Kevin prefers going out with Eddie rather than spend the night with Jackie and Zoey believes she is pregnant.
Jackie's life gets a little more complicated because of a security guard and O'Hara's longtime affair comes to light.
Unhappy about Eddie and Kevin's friendship, Jackie asks Eddie to stop spending time with Kevin. A pharmaceutical company rep provides Jackie with drugs.
Post-birthday party, Fiona busts her lip open on her cast, and Dr. O’Hara and Jackie stitch her up in the Peyton kitchen. Jackie notices Sarah Khouri’s philandering behavior and brings up her concerns to Dr. O’Hara. Libby Sussman (BARBARA BARRIE), the über-patron of All Saints, is brought into the ER. Before she can make good on the threat to pull her funding, she dies. Unnerved by Dr. O’Hara’s relationship, Jackie tells Eddie she needs time to reconsider their relationship – Jackie’s quality time with Kevin turns into a huge fight.
Jackie deals with Fiona's teacher's concerns and suspicions about her busted lip and cast. Dr. Cooper sets his friend Georgia up with Eddie. Dr. O'Hara, having once again ended things with Sarah, takes comfort with spending time with Jackie and her family in Queens. Jackie (and everyone at All Saints) is touched by the case of a determined man – John Poole (HARVEY FIERSTEIN) – who plants himself in the middle of the ER while he tries to let go of his dying husband. Kevin takes Grace to her first appointment with a psychiatrist. Eddie brings Georgia to Kevin's bar on their first date, where he runs into Kevin, Jackie and Dr. O'Hara.
Jackie tells Kevin she wants to send Fiona to Immaculate with Grace. Kevin makes Jackie promise not to accept money from Dr. O’Hara. Jackie rents a P.O. Box in order to safely receive her secret credit card bill that she’s now using to pay for prescriptions. Jackie lies to Dr. O’Hara and says Kevin agreed to accept her offer of money for the girls. Dr. O’Hara tells Jackie she needs to get an MRI of her back. During an unusually busy day at the hospital, Mrs. Akalitus jumps in to assist the nurses. After being back in the trenches, she decides to get rid of the Pill-O-Matix and bring Eddie back. Dr. Cooper's Tourettes kicks in, and this time he grabs Zoey's breasts in front of Lenny (LENNY JACOBSON) who punches him, breaking his nose. Jackie discovers that Grace's anxiety has led to an unusual disorder.
Jackie shows Dr. O'Hara a fake MRI to get an oxy prescription. Dr. O'Hara confronts Orthopedics and finds out that Jackie faked her MRI. Mrs. Akalitus rehires Eddie as the hospital pharmacist. Mrs. Akalitus and Jackie advise the wife of a patient to divorce him so that they can avoid going bankrupt and he can qualify for Medicaid. Dr. Cooper is distraught over the end of the "Face of All Saints" campaign and offers to pay for a new round of ad space. Sam invites Dr. Cooper to hang with his friends and his girlfriend after work. On Jackie's way home, she helps a businessman having a seizure and discovers baggies of prescription pills in his jacket — he's a white collar drug dealer. Jackie steals his stash from him while they wait for EMS.
Jackie unravels when she loses her pills on a family vacation.
After a disastrous family vacation, Jackie returns to work for a day of reckoning. The mounting pressures and conflicts in her personal and professional life reach a boiling point. Unexpected alliances lead to revelations that even Jackie can't avoid.