The Conner family is thrown back together in a haze of blood and confusion, as prodigal son Griffin returns to his second family home - Bethune General Hospital.
Griffin's first day as Bethune's newest porter is a rocky one, while Melissa forges an unlikely connection with the sister of a patient whose life she is scrambling to save.
Brian resolves to improve his patient interaction after receiving several complaints, while Griffin forms an unlikely bond with a cantankerous war veteran. Dr. Tuttle refuses to consider Sandy’s diagnosis of a rare disease in a dancer.
When two babies die of a mysterious infection in the Paediatric ICU, Allen scrambles to find patient zero before Bethune General suffers a full-blown outbreak.
Bruno shocks everyone by making an obscure diagnosis that saves a patient’s life, and a momentous secret from his past is revealed. After being kicked by a patient, Sandy calls Melissa for help instead of Brian.
An offhand comment from Allen sends Melissa into a tailspin, while Brian desperately tries to atone for a past mistake.
When Rebecca is brought into the ER with a mysterious paralysis creeping up her body, Allen has to scramble to find out what's happening before it's too late.
Griffin starts to spin out of control after a harrowing car accident evokes a traumatic event from his past and Bruno gives Mel some vital tips on purse string suturing.
A tumultuous day at the hospital gives way to an awkward dinner with Brian’s family, leading to an astonishing revelation for Sandy.
Sandy struggles to say goodbye to Brian as her reconfigured family rally around to support her. Zoe and Griffin organize a labour stoppage after Lonnie is fired.
Before Allen Conner can process losing his job as the head of Infectious Diseases at Bethune General Hospital (Beth-H), a massive explosion tears through the basement. Though he and Griffin work brilliantly together to treat those caught in the blast, the damage is catastrophic. Striking new ER resident Peter Cutler recruits Mel in aid of a foreign agricultural worker. Chief-of-Staff Linda Tuttle looks for a scapegoat in the wake of the explosion, while the downstairs staff grapple with loss, and Allen pursues a new position as an ER doc at Beth-H.
After Melissa Conner performs what should be a straightforward surgery on firefighter Renee Hudson, Renee is left in mysterious and agonizing pain. As Mel and Jerry retrace their medical steps trying to find the cause, the cracks in their relationship are exposed. Allen's first day in ER is complicated by the strange and violent behavior of Tyson “Pitbull” Danko, and Allen and Cutler need to work together in order to keep Pitbull in hospital long enough to find out what‟s really wrong with him. Griffin and Zoe pull together to help a still-reeling Kanaskie eradicate a bedbug problem at Beth-H.
As Griffin and Zoe adapt to being roommates, Griff porters around outpatient Jayne Baugher to her various appointments. When Jayne dies unexpectedly while under Griff's supervision, he is required to answer to an inquiry underway to assess his (and Beth-H's) liability. While Allen works to increase his efficiency in the ER, he is able to correctly diagnose a patient with a serious condition whom others have dismissed as merely an annoyance. And Sandy Conner, on her first day back from maternity leave, locks horns with her strict new supervisor Jason.
Zoe is blindsided when her mother shows up to Beth-H unannounced, just as she’s getting ready to start her shift. Zoe hasn’t heard from her in twenty years – and the more she learns about her mother, the better she understands why. Allen performs a heroic emergency procedure and saves a patient’s life, and must contend with the psychological aftermath. Griffin becomes overly involved when he tries to play matchmaker to a pair of love struck teenagers.
Mel’s new relationship with Cutler is causing a rift with Sandy, who recruits Rebecca to babysit against Mel’s wishes. Zoe has agreed to a bone marrow transplant to save her estranged mother, but Griffin is acting strangely and can’t seem to pull it together to support her. Mel, riding a high from her relationship with Cutler, takes an uncharacteristic risk in surgery. The whole Conner family is rocked when Rebecca’s first time looking after Maya results in crisis.
As Cutler tries to figure out where he stands with Mel and at Beth-H, a woman mysteriously goes into toxic shock and she and her husband must face the meaning of sacrifice. Mel catches Griffin involved in illicit activity and refuses to believe him when he swears he’s clean. Allen butts heads with the new Chief of Staff, while Sandy learns a valuable lesson treating a prisoner admitted to Beth-H.
When a peculiar woman turns up at Beth-H complaining of a migraine, Allen quickly discovers there is much more going on with her than a headache and he’ll need to employ all of his ID (Infectious Diseases) skill in the ER. Mel reattaches a reluctant construction worker’s severed hand while also contemplating what Cutler’s move to Dallas means for her. A patient of Sandy’s is refusing to eat, and Griffin’s misguided effort to help nearly leads to disaster.
When a police officer is killed chasing an urban explorer through an abandoned factory, Mel fights to save her wife – EMT Nicole Foster – who suffers a dangerous reaction to the devastating loss. Griffin reconnects with his old partner in crime Hugh, and together they set off in search of Griff’s ex-girlfriend Natasha. But when Griff finally tracks her down, it isn’t quite the joyous reunion he was hoping for. Allen pressures Kanaskie to get Griff’s job back, and Cutler tries to protect the urban explorer from overzealous cops he believes are out for revenge.
Mel and Cutler are slated to catch a flight to Dallas to plan their future there when Griff’s alarming behaviour holds them back. Sandy insists the Conners address Griff’s drug problem immediately as a family, despite warning signs that suggest they should utilize professional help. Meanwhile, Mel duels with her replacement, Dr. Jake Reuben, over the care of her cherished high school English teacher, and Cutler identifies a patient with critical symptoms that a distracted Allen has missed.
Sandy is in critical condition following a car accident on her way to find an unstable Griffin. Zoe tracks down a messed up Griff and peels him off the roof, but when she cleans him up and brings him into Beth-H to see Sandy, Allen is livid. Mel pressures Jake and Dr. Bernstein to deliver the best medical care possible to Sandy, and Cutler tries to help a family whose son is displaying bizarre and troubling behaviour. Through the darkness Allen and Griff are able to reach a measure of understanding, and Griffin ultimately turns to his downstairs family for help.
When medical supplies go missing in a basement storage closet at Bethune Hospital, Transport and Housekeeping Department supervisor Frank Kanaskie sets up a hidden camera to find who’s responsible.
