Dylan struggles with fatherhood and dating; Lu can't figure out why her 11 year old patient is constantly gaining weight.
Lu and Jonah's wedding day finally arrives, but not without complications; Meanwhile at Rittenhouse, Dylan is busy with a woman about to deliver twins and finds out his daughter has been arrested.
Dylan tries to get a transplant for a Down Syndrome patient; Lu finds out that several of her patients have had unprotected sex with an AIDS-infected man as a part of a gang initiation, as the staff wonders what is wrong with Lu's mood lately.
While Dylan is trying to save the life of the governor, Lu is actively pursuing her regarding a patient who is on death row. Meanwhile, Kayla seeks Dylan's advice as she treats a young pianist whose left hand has been severed. And weary from dealing with overwhelmed teen mothers, Peter starts a boot camp for teenage fathers. With Jonas out of the country trying to save his business, a pregnant and anxious Lu calls on the other two men in her life — Dylan and Peter — for moral support.
Lu must crack a puzzling mystery when her patient is accused of welfare fraud because her children's DNA doesn't match her own. On a personal front, the doc's life is equally stressful as she and Jonas find out that something might be wrong with their baby. Meanwhile, Peter makes a surprising discovery when he attempts to heal his injured shoulder with herbal remedies.
A 16-year-old girl is supposed to donate a kidney to her older sister, but she pleads with Lu to stop the lifesaving surgery. Having spent most of her life donating blood and bone marrow to her sibling, who suffers from leukemia, the teen can't bear any more procedures. The parents are furious, and Lu is caught in the middle of this family drama. But when the adolescent downs a bunch of pills, her older sister decides to call off the procedure anyway. Meanwhile, Kayla and George compete for the position of chief resident. Despite rumors that affirmative action was involved, Kayla gets the coveted job based solely on her merits.
When an out-of-state insurance company mandates that Dylan's patient be released less than 24 hours after having a mastectomy, he finds a way to get around the system in order to give this woman the proper care. Meanwhile, Lu's cerebral palsy patient decides to take legal action against her mother, who had smoked the entire time she was pregnant with her. And new dad Dylan enlists Lu's help in talking to his own daughter about quitting smoking and how he should approach the teen on the delicate subject of sex.
Lu works feverishly to save two patients in the burn unit, one a firefighter and the other an ugly duckling who has an adverse reaction to medication that's causing her skin to fall off. The pair is separated by a curtain but continue to talk and offer each other support; eventually they fall in love. Meanwhile, Kayla and Peter clash in the ER over how to handle the death of a teenage boy who died from heart failure. Eventually, they see eye to eye and work with the deceased's family to raise funds for the adolescent's deadly but detectable condition (hypertrophic cardiomyopathy).
Christmas at Rittenhouse finds Lu not only taking care of her own heavy caseload, but also treating Dylan's patients while he spends the holidays away with Araya. Lu's main priority is finding a home for three siblings who were abandoned by their meth-addicted mother. Meanwhile, a Santa with a Scrooge-like attitude visits the hospital.
When Lu's patient's appendix ruptures, she looks to Dylan to help her save the woman's fertility. Kayla tries to make amends with her estranged twin sister Keisha, but after she becomes unreasonably belligerent, Kayla begins to worry something more than sibling rivalry is troubling her.
Lu tackles a rare and deadly disease that does not respond to conventional treatment. Lu circumvents the insurance system for a far less conventional but much more effective medication. Dylan uses his faith to try and convince his patient to fight for her life.
Lu struggles to help a seriously ill pregnant woman without hurting her baby. Kayla pretends that a patient is alive to appease his unstable girlfriend, who says she has a bomb. Meanwhile, Peter looks for a missing boy, and Lana soothes an elderly man about to enter a nursing home.
Lu and Dylan are forced to confront an ethical dilemma when they begin using an experimental drug on a patient. Also, Dylan faces losing Araya to her maternal grandparents, who come to town hoping to make a fresh start with the teen and ask her to make a huge life decision.
In the series finale, Lu is forced to have a special delivery after she is trapped in a basement. With her medical guidance, Lu's husband, Jonas, performs an emergency c-section. Dylan struggles to save a gunshot patient who tells him the name of the gang member who shot her. After going to the police, Dylan realizes he may have put his family in danger