Cristina enlists Meredith to help her prepare an acceptance speech for her possible Harper Avery win and while Owen offers to attend the ceremony with her, she insists on going alone. Meanwhile, Derek feels overwhelmed between his responsibilities at home and at the hospital. April and Jackson come to a disagreement on children and religion, and Callie and Arizona try to reconnect in their marriage.
The hospital gets inundated with flu infected patients, which causes the doctors to slowly fall ill one by one. Derek must fight off the sickness as he prepares to give a speech on brain mapping and the residents place bets on who will fall ill first. Meanwhile, a new doctor at the hospital gives Alex a glimpse into an alternate form of medical practice.
It's Richard's birthday and Bailey invites him to scrub in on the case of a lifetime. Meredith hires a research assistant to help with her portal vein project. A scorned Callie gives Derek quite the shock. Meanwhile, Shane helps screen candidates for Cristina's clinical trial and meets a young expectant mother who needs his help.
Arizona has a bad day which escalates when she advises one of Callie's patients on a potential double amputation. Derek goes back on a promise to Callie, and Jo and Stephanie come across an abandoned baby outside the hospital. Meanwhile, the doctors deal with the repercussions of the non-fraternization rule, which include meetings with HR and one doctor's suspension.
After an anonymous complaint is issued by one of their own, the hospital implements a non-fraternizing policy causing the couples to panic. Meanwhile, Emma and Owen talk about the future, Cristina and Meredith enjoy a little girl time, and Richard enlists the residents to help research a rare cancer case.
On the day of April's wedding, the Grey Sloan Memorial doctors are all preoccupied with their own drama. Meredith and Cristina continue to argue about their research and careers, Bailey comes clean to Ben about her feelings regarding him moving back to Seattle, and Shane puts himself in a risky situation. Meanwhile, Derek gets a phone call that will change his life.
April’s sisters arrive to help celebrate April’s upcoming nuptials and quickly get on her nerves. Matthew and Jackson are forced to work together when they witness a terrible accident, Callie and Arizona work hard to reestablish their relationship and Cristina is pressured to live stream an upcoming surgery. Meanwhile, a familiar face returns to the hospital.
Ben worries that a casual conversation with Derek could potentially cause issues for Bailey, Cristina turns to Shane as tension grows with Meredith, and April's upcoming wedding makes for an uncomfortable situation between Jackson and Stephanie. Meanwhile, Meredith plans a Thanksgiving dinner at her house.
The doctors of Grey Sloan Memorial throw a fundraising gala which turns wildly competitive after Jackson makes a rash promise. Back at the hospital, Bailey’s patience is tested when she has to deal with several extremely difficult patients. Meanwhile, Shane and Stephanie handle an incredibly busy ER by themselves and Alex reveals an emotional secret to Jo.
The Grey Sloan Memorial Hospital doctors are faced with the devastation left by the storm. A giant mudslide in Seattle injures a group of first responders and citizens, causing the already short handed ER to spring into action. Meanwhile, Meredith is faced with a tough decision that will affect the life of a loved one, Callie is rocked by the reality of Arizona’s infidelity, and Richard’s life is in extreme danger.