Jackie is spending time with her family at the beach but still shows that she's in charge. At the hospital, Gloria is concerned with the growing disappearance of drugs and gets Jackie to give training to staff on how the properly use the dispensing system. Dr. Cooper lodges a formal complaint against her and she comes within inches of being shot when a deranged patient fires their gun at no one in particular. Eddie is still trying to contact her but she ignores him completely. Until he finds a way to get her attention that she simply cannot avoid.
Dr. O'Hara shows up at work still high on the Ecstasy she took the night before. Jackie deals with a young boy who may have a serious respiratory problem. His parents are thrilled when Jackie says they can do the necessary tests at All Saints but may have sent them home too early. Having recovered from his suicide attempt, Eddie visits Jackie's husband Kevin at the bar. Nurse Sam begins to ask if either Jackie or Dr. O'Hara have a drug problem. Dr. Cooper has taken to twittering and it's driving Jackie crazy.
Everyone at the hospital is put out - especially Dr. O'Hara - when Dr. Cooper is listed in a monthly magazine as one of the 25 best doctors in Manhattan. Jackie is less than pleased when Kaitlin shows up on a play date at her house. She's even less pleased when Kaitlin sees her snorting a line. At the hospital, she's almost caught taking drugs out of the dispensary using Zoey's access number. Back at home, she's dumbfounded when she sees who husband Kevin's new friend is.
Jackie is still incensed at having found Eddie in her house and tells him to stay away; he's not very receptive to the idea. Zoey performs brilliantly when a young child is brought in unable to breathe. A patient with stage 3 lymphoma is brought to the hospital but Dr. Cooper doesn't react well to Jackie's suggested treatment. She decides to help him out anyways. Dr. O'Hara and self-confessed sex addict Sam take it to the next level.
Jackie is mad a husband Kevin when he reveals that he went to the movies with Ginny Flynn and the kids during the children's play date. Jackie decides to sleep on the couch. At the hospital, Gloria Akalitus is still concerned about the seepage in the drug lockup and posts a security guard at the machine, which doesn't seem to do much good. Sam still pursues Dr. O'Hara, who saw it all as a one night stand. O'Hara also reveals to Jackie that she knows a famous international TV news correspondent. Akalitus asks Dr. Cooper if he will be the face of a new promotional ...
Jackie sleeps with Eddie at his apartment and tells him to stop seeing Kevin. Posters with Dr. Cooper's face are plastered all over the city, much to the disgust of Jackie and Dr. O'Hara. Jackie treats a female Iraq war vet with PTSD. Dr. O'Hara's ex, Sarah Khouri, comes to town and they're back on. With Eddie and the Pill-O-Matix becoming less reliable sources, Jackie finds ways to get pills. Eddie ignores Jackie's request and invites Kevin out. Jackie allows Fiona to have a fake cast on her arm for her birthday.
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, the uber-patron of All Saints, is brought into the ER.
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 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.
After avoiding Eddie, O'Hara and the drug dealer who has come looking for his stolen pills, Jackie takes off early for a family vacation upstate. But when Jackie misplaces the stash of pills she brought to get her through the vacation, she starts to unravel bit by bit.
After a disastrous family vacation, Jackie returns to work for a day of reckoning. The mounting pressures and conflicts in her personal and professional lives reach a boiling point. Unexpected alliances lead to revelations that even Jackie can't avoid. Between Dr. O'Hara, Eddie, Kevin and the drug dealer, the wagons are circling around Jackie Peyton.