Meredith Grey è una giovane ragazza di Boston che, dopo la laurea in medicina, riesce ad entrare nel gruppo di tirocinanti di chirurgia del Seattle Grace Hospital. Si trasferisce così a Seattle, nella vecchia casa appartenuta alla madre. Qui si ritrova a condividere questa nuova esperienza insieme ad un gruppo di giovani coetanei, tutti alle prese con i più svariati problemi. Meredith è figlia di Ellis Grey, una famosa dottoressa specialista in chirurgia generale, e sente molto il peso del suo cognome. La sera prima di iniziare il tirocinio, Meredith incontra in un pub Derek, un affascinante uomo con cui passa la notte; solo il giorno dopo scopre che in realtà lui è Derek Shepherd, neurochirurgo dell'ospedale, nonché suo supervisore. Meredith deve così districarsi tra lo studio e il lavoro per poter diventare un chirurgo, e i sentimenti che prova per Derek.
Meredith rethinks her plans. The interns are on thin ice following a patient's death. Simone and Lucas are immediately tested in an emergency. Richard confides in Bailey. Teddy's fate is revealed.
Bailey tells the interns they must complete dozens of basic procedures before being allowed back in surgery; things are awkward between Simone and Lucas; Amelia comes up with a solution to a complicated surgery.
Meredith and Amelia work to secure funds for their research while Amelia finds herself at odds with a new attending. Levi runs into someone from his past, and Owen gives Winston advice. Lucas ditches Mika, forcing her to treat a patient alone.
Dr. Arizona Robbins returns to Grey Sloan for a particularly complicated case. The interns are interrogated about their past mistakes, while Teddy is eager to return to work after her health scare.
It's all hands on deck at Grey Sloan when a group of medical students is injured by a floor collapsing at their white coat party. Jo and Link are forced to talk about the future, while Jules confronts Winston about his attitude.
Mika and Teddy receive a patient from a nearby penitentiary. Catherine pushes back on Link and Monica's treatment plan for a VIP. Bailey tries to integrate wellness into the residency program.
An unexpectedly complex case brings back painful memories for Simone. Jules and Blue make a high-stakes bet on who can finish their procedure log first. Richard suspects Winston is avoiding him.
Owen and Teddy have the day off but encounter an injured civilian. Monica enlists Amelia's help with an operation on a young patient. The interns complete their procedure logs, allowing them back into the OR.
Just as Amelia comes to a realization, Teddy encourages her and Meredith to speed up their Alzheimer's research over fear of Catherine finding out. Mika finds herself caught in the middle of Link and Jo; meanwhile, Lucas receives bad news.
Wildfires threaten the Seattle region, leading to a flood of patients and emergency procedures. The doctors juggle overcapacity in the ER, complex surgeries and personal stress. Meanwhile, Meredith makes a rash decision that can't be undone.
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