The doctors work with the Center for Disease Control and Prevention to find an antidote to the deadly viral outbreak at Angels Memorial. Also, Leanne makes a life-changing decision, and Jesse welcomes a new batch of residents.

Guthrie becomes the hospital's new chaplain and considers undergoing a risky surgery to treat his Parkinson's. Meanwhile, the doctors treat patients involved in an apartment fire.

Angels Memorial descends into chaos when a plane crashes into the 8th floor. Also, Noa has a car accident and it is up to Mario to save her life. Also, Willis admits to Rox that he needs her in his life and the doctors gather in court to support Leanne for her custody hearing.

The ER is quarantined when a viral outbreak jeopardizes the lives of the doctors and patients at Angels Memorial. Also, Ariel, the young girl Leanne bonded with a year ago when she lost her father, returns to Angels.

When the lead actor of the musical “The Lion King” tour arrives at Angels Memorial with a throat infection, Leanne gives him a diagnosis that puts both his career and life in jeopardy. Also, the doctors and the cast of “The Lion King” help a 17-year-old boy deal with the difficult decision of taking his father off life support,

Leanne becomes rattled at the thought of losing Jesse, as he fights for his life after suffering a massive heart attack. Meanwhile, Mario asks the residents to cover for him so he can search the city for a patient’s son, which goes against Neal’s direct order not to leave the hospital

After a violent incident inside the hospital results with some grave injuries, the doctors are questioned. Christa and Neal admit their relationship to human resources.

Heavy fog at the scene of a massive multi-vehicle accident puts the doctors in danger; Jesse's confidence has taken a hit; Carla's condition turns critical.

Malaya must inform a college student who regains consciousness at Angels Memorial that she's the victim of a rape. Meanwhile, Willis and Campbell butt heads over a terminally ill woman who wants to end her life on her own terms; and a comedian is treated after he collapses on stage during a performance.

Neal clashes with his neurosurgeon father over how to treat his gravely ill mother, whose mysterious symptoms force Angels Memorial to quarantine Trauma One.

The doctors must race to save a girl caught in the crossfire of a shoot-out; Willis shifts his focus to field medicine, choosing to work primarily on an ambulance with his new partner, paramedic Rox; Leanne begins her journey to adopt Ariel.

Max is brought to Angels Memorial with breathing difficulty, and Ariel tells him she loves him. Also, Rox accompanies Willis and Martin to the funeral of an army buddy of Willis' brother, and Willis decides to get to the bottom of what happened to his brother's unit.

While rescuing an injured firefighter, Rox is hit by a drunk driver and rushed to Angels Memorial. Willis begins to realize his feelings for Rox and goes to great lengths to help her. Also, Leanne is excited to tell Ariel good news about her adoption.

Willis continues to tend to Rox's medical needs in San Diego and Leanne and Max's father go searching for Ariel. Also, when Noa reveals to Mario she wants to take a job offer in Philadelphia, and Campbell offers Mario the attending position at Angels, they realize their career choices will mean ending their relationship.

On Halloween night, Willis, Noa and Elliott rush to the scene of a fire at a haunted theater, where Dr. Nolan and her boyfriend’s son are trapped,

A 13-year-old girl arrives at Angels Memorial following a seizure caused by spina bifida and the doctors are shocked to learn she is Campbell's daughter. Meanwhile, a workaholic deaf patient and her translator are treated after their car rolls into the Los Angeles River.

A code black at Angels Memorial takes a turn for the worse when a city- wide blackout leaves the hospital without power or back-up generators. As Campbell and Leanne divert high-risk patients to a nearby care center, Elliot and Heather are trapped in an elevator with a woman in labor, and Willis and Dr. Nolan try to help a 92-year-old woman who thinks it’s 1942.

Leanne visits a prison to finally confront the drunk driver who killed her family. Meanwhile, Malaya begins to feel uncomfortable around her patient.

Over the radio, Leanne and Jesse talk a young girl through how to use the supplies on board a small plane to build a makeshift defibrillator when her mom, the pilot, loses consciousness mid-flight. Also, Rox and Willis are taken hostage at gunpoint while on their way to meet the plane at the landing site.

Willis and Rox are called to the scene of a wildfire in the mountains of Los Angeles to tend to the injured firefighters, and they choose to stay to look for a missing young boy who was separated from his father in the chaos.

Leanne must deal with the difficult decision of whether to save Tom Moreno (Michael Trucco), the police officer who helped her during her family's accident, or his shooter, who has more serious injuries. Also, when Malaya's pregnant ex-girlfriend, Carla Niven (Shiri Appleby), arrives at the hospital with pain in her arm, Malaya is shocked by her MRI results.

As the doctors treat patients from the chaotic multi-vehicle accident, a love triangle begins to build between Mario, Angus and Heather. Also, when Malaya learns that Carla is at the hospital, she goes against Carla's wishes and stays by her side during the delivery of her baby. Shiri Appleby guest stars.

Angus' older brother, an "all-star" ER doctor, tries to secure a position at Angels Memorial. Meanwhile, Christa's romantic feelings towards Neal begin to grow; and Malaya deals with a patient who is obsessed with her.

Willis must help a promising soccer player make a life-altering decision after he's seriously injured, and another patient's hesitation to share that she's transgender makes it difficult for the doctors to diagnose her severe abdominal pain.

Jesse is in denial when his brother arrives at Angels Memorial in bad shape after being pinned down in a warehouse collapse and further tests reveal he has advanced congestive heart failure. Also, Willis opens up to Rox about his brother who was killed in Afghanistan.