Meet Meredith Grey. Daughter of famous surgeon Ellis Grey and currently recovering from a one-night stand. She shoos away her evening's companion, saying she'll be late for her first day of work. She is a first year intern at Seattle Grace Hospital and is working alongside some colorful characters. Cristina Yang is a highly competitive Stanford graduate who befriends Meredith. George O'Malley is a quirky warm hearted man who learns a lesson or two on his first day. Izzie Stevens is a former model who doesn't get any special treatment on her first day. And Alex Karev is an arrogant jerk who misdiagnoses a patient on his first shift. Overseeing them is Miranda Bailey, (not-so-) affectionately dubbed 'The Nazi'. Meredith also gets a surprise when she realizes that her friend from the night before is a co-worker, and even worse, her boss.

The surgical staff tries to be optimistic as a young woman clings to life after a brutal attack. Meanwhile Meredith puts her career on the line to save a newborn in the hospital nursery, and the other interns learn that it takes more than just medical knowledge to be good at their jobs.

While George is feeling a little less masculine because of the way Izzie and Meredith have been treating him (like a sister), Izzie is assigned to a patient about to loose all of his masculinity. Cristina, true to her competitive spirit, shows up early and assigns herself to an ill woman, who happens to have been Meredith's moms scrub nurse. Alex, meanwhile, is busying himself copying and pasting pictures of Izzie's racy magazine spread all over the interns' locker room. And while Meredith is trying to cope with her mother's Alzheimer's, Derek treats a patient who has managed to get nails stuck in his head.

Meredith realizes that she must take on a lot more responsibility when she is told that her mother needs to sign over all of her assets to her. As Izzie prepares to have a party for her boyfriend Hank (the scale of which is unknown to Meredith), Meredith has her first heart surgery. During the surgery she fears that she has fallen asleep and damaged the patient's heart. Meanwhile, Cristina and Burke hit it off. At the party, Meredith and Derek get caught together by Dr. Bailey.

Cristina and Meredith try to figure out if Cristina should tell Burke that she's pregnant right before Cristina faces an emergency. Alex and Izzie get closer while Meredith's mother gets too close.

As Cristina tries to recover, she proves to be a very difficult patient, and a visit from her mother doesn't improve her demeanor any. And Meredith's mother, Dr. Ellis Grey, has the hospital staff running in circles.

Cristina goes right back to working right after being discharged. Izzie isn't talking to Alex. Derek and Meredith treat a patient. George and Alex get stuck in an elevator.

Cristina is bothered by a new year's mandatory work limit. Izzie patient, Denny Duquette, wants two things: 1. a heart transplant, 2. Izzie. Addison detests Derek's trailer, Derek visits Meredith's mom, George treats a young teen hermaphrodite frustrated by her pre-pubescence. Other news includes patients doing uncanny things and relationship havoc being wrecked between the doctors, as per usual.

All the nurses at Seattle Grace Hospital go on strike, leaving the doctors to fend for themselves. George refuses to cross the picket line and finally joins the nurses on their strike while Alex, Cristina, Izzie and Meredith meets Bailey's stand-in: Dr. Cindy Aaron, the complete opposite of Miranda Bailey. Izzie agrees to work on a difficult pregnancy case with Addison, while Cristina and Alex are in the pit attending to a young married woman with a real bad case of rash. Meredith happens on an old woman that she needs to intubate and then learns she was DNR.

Derek and Addison's relationship is rocked to the core when a former friend comes to Seattle Grace and his presence promises to shake things up for a few members of the staff. Burke and Cristina's relationship is affected when one of her secrets is outted. Alex and Izzie are having similar reactions to their closet scenes during the Code Black crisis. On top of this a cocky doctor shows up to piss Derek off in all kinds of ways. A patient is suffering from constant orgasms and her condition sparks interesting conversations among the staff. George is trying to figure out how to get Meredith to see him as more than just a housemate. Another patient, that Derek is treating, is dealing with a rare disorder and needs his parents support and understanding. Burke has a patient who inspires him to talk to Meredith and Cristina about doing what they say they will. Meanwhile, Meredith learns more about her family (in fact maybe more than she may have wanted to know) through her parents.

Meredith must make an important choice about which path she wants to follow to determine the future of her love life. While she considers her future she and others have flashbacks of their pasts. Cristina spends time with Burke while he recovers. Webber and Adele have a conversation after he spends the night at the hospital. Everyone attempts to deal with Izzie's choice to quit. George seeks relationship advice from Derek.

George's father has a serious heart problem that requires surgery and George chooses Burke to do the procedure. Burke doubts himself because he knows the pressure this kind of surgery will put on him, but Cristina believes the team can handle it. Derek works with Meredith on being a couple again and tries work with Addison on more civil terms. A patient has had mutiple plastic surgeries so that his girlfriend will like him more. A mom wants her daughter's babysitter fired, after she is brought in with multiple injuries, but the girl likes the babysitter more than her mother.

Recent events strain Burke and Cristina's relationship. Mark and Derek must work together when two close-knit brothers seek medical help. One of Meredith's half sisters is admitted to the hospital.

The race for the Chief's position is on, and the attending physicians, Derek, Burke, Addison and Mark, compete for Richard's affections by trying to help out everywhere possible. The Denny Duquette Memorial Clinic is open for business, but only one single patient shows up. Izzie is disappointed in what she invested Denny's legacy in, and tries to steal patients from the emergency room. Callie and George get back from Las Vegas, announcing their marriage, much to everyone's disbelief. Izzie is not supportive of their marriage and tries to get George to realize the mistake he has made. Meanwhile, Meredith's Alzheimer's-stricken mother, Ellis Grey, experiences a change in her medical condition by becoming lucid for the day. She is disappointed in the mediocrity her daughter has fallen into and begins to despise Derek, blaming him for what happened to the Meredith that used to be "a force of nature". Ellis has to have heart surgery and, despite her wishes, Meredith schedules her upcoming surgery. Richard talks to Ellis and realizes that she is still in love with him, but loses her memory after their talk ends, before Meredith has the chance to tell her how she really feels.

A mass trauma situation, which turns out to be a ferryboat accident, challenges the whole staff of Seattle Grace Hospital. Richard finds difficulty in coping with his separation from his wife and dyes his hair "for the ladies", which becomes an internal joke between Mark, Burke and Derek. Cristina tries to tell Meredith about her upcoming marriage, but doesn't have the strength to. George promises to find a woman's son, who has been separated from her at the accident. The woman refuses to go into surgery until she is assured that her son is alive. Izzie has to take care of a man who got stuck between two cars on the ferry, but nobody helps her due to the large number of injured people. Alex rescues a pregnant woman with severe wounds on her face, and promises to take care of her. Meredith looks after a girl who has been separated from her mother after the accident, but accidentally falls into the water and drowns, with nobody but the little girl as a witness.

Meredith is still underwater, but nobody seems to notice. Her worsening condition makes her rescuing an urgent matter. Derek finds her coat on a man she had helped, and starts looking for her and, much to his shock, the little girl Meredith took care of suggests that she is in the water. Derek saves her, but she is almost dead, due to hypothermia. Izzie has to perform brain surgery on a man stuck between cars, as he begins to experience seizures. She drills holes into his head, perforates his skull and ultimately saves his life before he is rescued and transferred to Seattle Grace Hospital. George lies to the woman whose son he had been looking for, in order to get to surgery, but still doesn't have any luck in locating him. Alex finds no hope in searching for the pregnant Jane Doe's family as she undergoes surgery. The interns find out about Meredith's situation and express their hopelessness. She wakes up in what appears to be limbo and meets her deceased acquaintances.

Everyone is pushing for Meredith to survive, or in this case to be revived. People are still dealing with the fallout from the ferry disaster. A young man named Lucas is having problems with brain-mouth coordination. Someone else dies.

As Meredith puts Zola to bed and falls asleep, she begins to wonder -- what if her mother had never had Alzheimer's and she'd had loving, supportive parents? The reverberations of a happy Meredith Grey change the world of Seattle Grace as we know it. What if she had never met Derek in that bar and he had never separated from Addison? What if Callie and Owen had become a couple long before she met Arizona? And what if Bailey never evolved from the meek intern she once was?

With Cristina gone, a new doctor, Maggie Pierce, making the rounds and Derek wanting to move to Washington DC, Meredith struggles to regain a sense of normalcy both at home and in the hospital. Meanwhile, Callie and Arizona come to a decision about surrogacy, Amelia overhears a big secret, Bailey realizes she will have to fight Alex for Cristina’s board seat and a freak accident causes two teenagers to be caught in a very compromising position.

Secrets from Ellis Grey’s past come to light when Meredith watches old videos and reads through her mother’s journals. Meanwhile, Maggie rocks the hospital with an unexpected announcement; Alex gets new responsibilities and Callie focuses her attention on the Veterans’ project.

Meredith and the staff feel the impact of losing one of their own; Jackson struggles with April's decision; Bailey and Ben argue about their future. Months after Derek's funeral, Amelia struggles with her emotions; April plans to return; and Derek's part in Meredith's life continues to grow.

After a roller coaster car falls off the track at the county fair, the doctors at Grey Sloan tend to patients who spark memories about ghosts from their past. The series 300th episode!

Meredith has a patient whose family is celebrating Day of the Dead, making the doctors remember loved ones they have lost. Richard shares unexpected news with Meredith about her father, Thatcher. Meanwhile, Teddy tries to tell Owen that she is pregnant but they get sidetracked, and Jo encourages Link to pursue one of the doctors.

Meredith finds herself having to side with either Alex or DeLuca during a difficult situation, but she doesn’t want to betray either of them. Meanwhile, Maggie reveals details about her personal life that cause a public stir, and Levi struggles with whether or not to tell his family about Nico.

As the city of Seattle revels at the Phoenix Fair celebrating the city’s rebirth post-COVID, the Grey Sloan doctors treat a patient who encounters illegal fireworks. Meanwhile, Bailey has her sights set on hiring new doctors, but she’s having trouble finding viable options. Owen and Teddy attempt to take the next step in their engagement, and Meredith has a surprising opportunity when she meets a dynamic doctor from her mother‘s past.

The crossover starts on Station 19 S05E01 Phoenix from the Flame (I).

Nick whisks Meredith away to his Minnesota cabin for a romantic weekend, leaving Winston and Maggie to care for Meredith’s children. Meanwhile, Amelia and Kai grow closer.

Due to a blood shortage, Grey Sloan Memorial is setting up a voluntary donation center. Meanwhile, Nick asks Meredith for help with his patient and Winston is hung up on his relationship with his brother.

With Levi’s help, a patient celebrates a milestone. Jo processes a difficult diagnosis, and Maggie and Winston decide their future.