While Amelia and Owen's wedding continues, Andrew is brought to the ER after being assaulted by Alex, leading Meredith and the other doctors to the hospital to help. Meredith faces a dilemma about protecting Alex or telling Bailey the truth about the assault. Meanwhile, April and Catherine Avery clash about naming the new baby. Nathan and Meredith continue to work out their relationship at the same time as they try to hide it from Maggie, who is affected by Andrew's assault. In the end, Meredith tells Bailey the truth, but not before Alex turns himself in to the police.

On Andrew's first day back, Alex is charged with felony assault in the second degree. When he's distracted at work, a kid's newly transplanted kidney ends up jeopardized, causing Bailey to decide that Alex can no longer work as a surgeon and demote him to work at the Denny Duquette Memorial Clinic. April has trouble letting go of Harriet, who gets to go home with Jackson. Jackson asks April to move in with him so she can recover. Stephanie proves to be a good friend to Jo, who tells Alex she doesn't want to be with him after what he did. Per Meredith's request, Nathan turns Maggie down when she finally asks him out, but Maggie's not planning on giving up just yet.

A male patient is wheeled into the OR where Meredith, Owen, and Stephanie are waiting. Meredith has been up for 48 hours and Owen at least as long. Richard shows up to help having napped all day. Richard wants the patient to be given a name; he picks Gail, a cello player and music teacher. Each of the doctors has a flashback to a tragic incident from their past. Owen flashes back to working with his sister. She tells him to cut it out, meaning the liver, and he does. Stephanie is asked to contact UNOS to get the patient added to donor list. Stephanie determines the patient has an autoimmune disease, ITP. The doctors argue as to what needs to done at each stage in the OR. The patient is identified as Carl Henley from a photo they took of him to show a woman who called about her husband. Gail was Richard's mother, who had pancreatic cancer and died when he was ten. Meredith eventually suggests using part of Carl's own liver, calling it a hail Mary. The repaired liver is put back in, before moving him to the ICU. Meredith apologizes to Richard for the things she said.

On the day before Alex's trial, Bailey, Arizona and Jo drive with medical equipment including an advanced ultrasound machine to a maximum security women's prison hospital to treat a violent teenage inmate and her unborn baby. Jo bonds with the inmate, who says that she had good times with her mother in the past and that her mother will be taking care of the baby for her until she is released. However, her mother is downstairs and tells the doctors that her actual plan is to adopt the baby. The doctors wrestle with whether to tell the inmate about this news, given her violent tendencies. When the inmate goes into labor she demands to see her mother. Jo finally says that she is downstairs but refuses to come up, and the doctors help the inmate through the delivery. Later Arizona scornfully tells her mother that the delivery was a success, and asks whether she will abandon this baby too if she turns out bad. Meanwhile, Bailey learns about the realities of patient care in a prison environment. On the way back home, Bailey tells Jo that Alex plans to take the plea deal and will be going to jail, which makes her throw up.

Dr. Minnick implements phase 2 of her teaching plan, where two residents a week get to lead a surgery from start to finish. Ben's first experience is ruined by Bailey and Webber arguing and Stephanie's 9-year-old patient dies. Stephanie is comforted by Webber, while instead of teaching her how to deal with loss, Eliza flees. Arizona learns that she's never lost a child before and comforts her. April steps in as interim Head of General Surgery but the attendings give her the cold shoulder, especially Maggie, who believes April deserted Webber and is now on Bailey's side. April and Maggie are forced to work together on a patient of Meredith's, who's reluctant to have a surgeon she doesn't know operate on her. Catherine bonds with April and takes her out to dinner to celebrate her new job.

April and Jackson travel to Bozeman, Montana to perform a throat transplant on a girl, leaving Harriet with Catherine. The two discover they still need to get consent from the donor's heartbroken father, for which Jackson uses his experiences with fatherhood. However, when a lesion is discovered on the donor, the transplant is off the table, meaning a laryngectomy is the girl's only option despite her parents' objection. April discovers that Jackson took the case because his father owns a diner near the hospital, and encourages a distracted Jackson to go talk to his father so his head can be in the game for their patient. Jackson does so and discovers that his father left because being an Avery didn't fit him, and that he has a happy life and never actually missed his son. Jackson comes up with a solution for the girl and he and April pull it off. They end up sleeping together and agree that this was the reason Catherine had Meredith switched for April. Before returning to Seattle, Jackson goes to tell Robert that despite being glad to have met him, he's not actually his father.

A spot on a scan alongside her chest wall causes a downward spiral for Maggie's mother. After surgery to remove the left-behind mass, Diane is found to have a metastasis in her liver. Meredith refuses to operate while Maggie thinks it's the way to go, resulting in Diane firing Meredith from her case. Bailey does the surgery when Maggie gets her hopes up about a trial, which Diane enrolls in after the successful surgery. Despite all the side effects, Diane has a good day and she teaches Maggie to cook lasagna, but she starts coughing up blood during a dinner with Maggie's friends. Richard fixes the esophageal tear in surgery, but Diane's health continues to deteriorate. Diane thinks Maggie will be hurt if she stops fighting, but Richard convinces her that Maggie's strong enough to handle it. Diane then stops the treatment and, after imparting wisdom and offering advice to her daughter, she passes away. Richard realizes he's not a father figure to Maggie and calls in Bill Pierce to comfort her. He also buries the feud with Bailey. Nathan and Meredith agree their timing's off and decide to postpone their promised dinner as Maggie would need Meredith to be there for her.

Stephanie and Andrew have to take care of intern Isaac, who has abdominal pain and insists it's not "internitis" as Stephanie thinks. Maggie teams up with Arizona to remove a delicate tumor from a fetus's chest while her colleagues worry she's not ready yet, given it's her first day back. Meredith agrees to hang out with Nathan to see if it could go somewhere before she tells Maggie. When Nathan finds out about her and Eliza, Arizona befriends Nathan and gives him some well-intended advice about dating Meredith. Richard and Bailey begin to work things out between them while Jackson attempts to console a distraught Maggie.

Nathan and Meredith end up on a flight to a conference together. She tries to ignore his moves but ends up having sex with him in the bathroom, insisting it doesn't mean anything. After heavy turbulence hits, Meredith and Nathan tend to the injured while receiving help from Harrison Peters, a pediatric dentist. In a quiet moment, Meredith tells Nathan about her own plane crash and losing her sister Lexie. One of their patients starts showing signs of an epidural brain bleed while the pilot is unable to land the plane because it's caught between two storm systems. Meredith continuously has to relieve pressure on the man's brain with a needle and syringe on the shaky plane, while Nathan has to save a man with pulmonary hypertension. When the plane finally lands, Nathan questions how Meredith can still be scared of letting go of Derek and starting something with him. She then decides to ignore her fear of yet again losing someone she cares about, and agrees to give it a chance.

April, Andrew, Stephanie, and Richard have bad news for their patient and her new boyfriend when she turns out to have worms breeding in her intestines. Bailey enlists April's help to get Catherine and Richard back together, but it turns out that Bailey's similarity to Catherine is the key. During a press conference about the events on the plane, Maggie derives that something happened between Nathan and Meredith. Meredith tries to explain things to an angry Maggie and ask for her forgiveness. Alex's pregnant patient with pancreatic cancer from the Clinic returns to the hospital. Her cancer has metastasized to her spine, messing up the parents' plan for the future. The case strikes a chord with Amelia in particular.

April and Meredith discover that their patient has an inoperable heart tumor, which the patient already knew about. While the woman has made peace with it and has resorted to having as much good sex as she can before dying, Maggie can't let it go that easily. However, she comes to realize that there's nothing she can do. Inspired to do what's good for her in the moment, Meredith removes the tumor and post-it from her bedroom wall and takes Nathan home with her. Eliza and Arizona have sex after a whole day of anticipation. Richard has to second Eliza's statement that Ben has been playing it safe lately, while Stephanie lets her anger take over when a religious father threatens to sue the hospital for operating on his son's life-threatening tumor without his and his wife's permission. Andrew plans to tell Jo about his feelings, but she stops him since she already knows.

Alex hires a private investigator and finds Jo's husband, Paul Stadler. He attends a conference where Paul is speaking, but he realizes that whatever he does will end badly for either Jo or himself and opts to let Paul go without a confrontation. Owen receives news that his sister was found in a basement after a raid in a rebel-led neighborhood. Amelia supports him and calls Teddy to verify Megan's identity and secure her transfer to Grey Sloan. Back at the hospital, the doctors are thrown for a loop when they discover that their half-naked car accident victims aren't a couple, but instead a woman who drove off the cliff on purpose to avoid getting raped. This discovery comes too late for Stephanie, whom the rapist has captured to secure an easy way out of the hospital. When the hospital lockdown traps Stephanie and Erin, a young girl wandering around the hospital, with the rapist, the rapist starts a fire to open the doors. Stephanie seizes the opportunity and sets the man on fire, but he drags himself towards gas tanks in a lab. Just as Stephanie goes to drag him away, the tanks explode.

As the flames rage throughout Grey Sloan, Bailey issues a mass-evacuation while Jackson and Meredith desperately search for Stephanie and Nathan. Stephanie, who is revealed to be alive, is forced to perform a surgery on Erin's leg, while the flames grow even bigger and looms closer towards the duo. Meanwhile, Owen and Amelia continue preparing for their journey, despite finding out about the incident at the hospital, to visit Owen's MIA sister, Megan. Back at the hospital, Stephanie is forced to go to extremes as she braves the growing flames on her floor, ending up in the staircase. Crawling towards the roof access with Erin in tow, Stephanie comes to the horrifying realization that her key card is missing, which is needed to open the door. Seeing no other option, she wraps Erin in a water-soaked blanket as she prepares to sacrifice herself. But just as the smoke reaches her, she sees that her key card is within sight and fights to retrieve it. As Stephanie and Erin at last enter onto the roof, Erin codes leaving Stephanie hysterical for help. As Stephanie is performing CPR while screaming for assistance, Ben leads a group of firefighters towards Stephanie's location, finally rescuing her at last. In the aftermath of the blaze, Eliza is fired by Bailey after an inquiry regarding the fire. Erin is alive and in recovery, and Stephanie is recovering from her burns as she tearfully tells Richard she's quitting. Nathan learns about Megan from Meredith who encourages him to reunite with his true love. Maggie is told by April that if she wants she could see Jackson. Owen and Amelia finally arrive at Madigan Army Medical Center as Megan's helicopter lands and she is pulled away on a gurney towards Owen, as he at long last comes to terms that his sister is truly alive.