Veteran emergency room nurse Jackie Peyton navigates the traffic of Manhattan's All-Saints Hospital, embracing a subtle drug addiction and making tough and sometimes unethical and even illegal decisions for the "good" of her patients.
With Sweet 'n All packets full of ground-up Percocet to get her through the day, Jackie shifts blame for the resurfaced flushed ear on rookie Zoey, and must swallow her pride and tell Coop that he had been right about diagnosing a patient's unlikely aneurysm.
Kevin shares his concern regarding Grace's mounting anxiety with Jackie. At work, Jackie must deal with a dying man (Eli Wallach) who refuses further treatment, while Eddie faces the possibility of being replaced by an automated dispensory. Meanwhile, Zoey must work up the courage to ask for her new stethoscope back after Dr. O'Hara takes it.
Jackie and Kevin are rattled by concerns raised at a school meeting regarding Grace's psychological development. Zoey, lamenting a day of "unexciting" cases being assigned to her, ends up dealing with a key, tragic "first" every nurse must overcome.
It's a topsy-turvy night shift for the All-Saints staff. Jackie bucks the system to assist a 10-year-old girl caring for her lupus-stricken mother, while male bonding between Eddie and Dr. Cooper puts a damper on Jackie's usual mid-shift tryst in the pharmacy back-room.
A fellow nurse and old friend of Jackie's checks into the hospital with terminal lung cancer, and asks Jackie to help end her life; Dr. Cooper's mother is admitted with a gall bladder attack and reveals a family secret about her son's upbringing.
A man is admitted to the ER with a steak knife in his chest, after an attack by the ex-husband of a woman he was dating for the first time; Mrs. Akalitus takes charge of a foundling abandoned at the nurses' station; O'Hara has a personal crisis Coop finds out that Jackie has a child.
Jackie discovers that a new temp nurse is abusing drugs, but when she confronts him, he calls her on hypocrisy; Mrs. Akalitus still has the foundling infant left at the hospital; Coop reveals to Eddie that Jackie has a child.
Jackie admits a dying patient she has treated before, learns that O'Hara has betrayed her secrets to a sister in Paris, suffers a drug-induced nosebleed, and forges an organ donation form in Coop's name; the parents of the baby that Akalitus is raising come forward to reclaim their child.
Jackie makes an unusual ploy to get Coop off her back about the fake organ donor card; O'Hara helps Jackie remove her wedding ring before a quickie with Eddie; Jackie begins mother-daughter dance lessons with Grace.
Eddie is replaced by an automatic pill dispensing machine; Zoey administers the wrong dose of a painkiller to a movie critic, who lapses into a coma. Jackie gets tossed out of the mother-daughter dance lessons after a clash with a mother whom she knew from her high school days.
Kevin invites Jackie to a midnight rendezvous in order to give her a new wedding ring; the comatose movie critic wakes up but his tastes have radically changed; Eddie learns the truth about Jackie's family; O'Hara's dead mother is admitted secretly for a post mortem.
After breaking up with Eddie, Jackie tries to reconnect with her family. However, Jackie is soon on the verge of losing it when Coop files a formal complaint against her, Eddie overdoses and she runs dry of drugs.
Jackie cuts through red tape to speed up a boy’s diagnosis, irritating Dr. Cooper, who has taken to Twitter as a way to vent. Mourning her mother’s death, O’Hara shows up after a night of clubbing, and Jackie covers for her while she comes down from Ecstasy. Eddie visits the bar and continues his friendship with Kevin.
Coop makes New York Magazine's Top 25 Doctors list, giving him reason to gloat and flabbergasting most of the staff. Jackie faces new challenges at home and at work with Grace's escalating anxiety and Jackie's increasingly conspicuous drug abuse. Eddie breaks boundaries and gets too close for comfort.
Jackie—in the midst of dealing with Eddie's intrusion into her home life—recommends an alternative remedy for a cancer patient who isn't responding well to chemotherapy. Dr. O'Hara covers for Zoey after she breaks the rules to save a young boy's life, and gives Sam an outlet to channel his addiction without turning to drugs.
Coop sets up his friend Georgia on a date with Eddie, who takes her to Kevin's bar; Grace attends her first session with a psychiatrist; a determined man refuses to leave the emergency room until he says goodbye to his dying husband.
In order to keep her credit card a secret, Jackie sets up a P.O. box for the credit card bills. In the meantime, Mrs. Akalitus invites Eddie to come back as the hospital's pharmacist. Jackie realizes the seriousness of Grace's condition.
Jackie manages to evade O'Hara's questions about her fake MRI. Jackie, Kevin and the girls have an unsuccessful trip. On the journey back, Kevin finds out that Jackie took O'Hara's financial gift but thinks it is for the girls' education.
Jackie's back at work after an aborted family vacation, and her indiscretions have put her at odds with her family, friends and coworkers. Complicating matters for her, she is being pursued by the drug dealer she ripped off.
Jackie and Kevin have an altercation over his recent discovery but Jackie denies being an addict. Jackie returns to work where O'Hara gives her the cold shoulder. Zoey has since slept with Lenny and animosity is still rife between Coop and Sam.