Amelia Shepherd is the youngest sister of Dr. Derek Shepherd, and like her brother, an excellent neurosurgeon. Her ambition to prove herself equal to her brother is only surpassed by her surgical skill. After graduating in the top of her class at Harvard and completing her surgical residency at Johns Hopkins, she comes to Los Angeles on a medical case and decides to stay after she is fired from her fellowship. She asks Naomi Bennett for a job when the two practices merge. She has known Dr. Addison Montgomery for many years and views her as a close friend and surrogate sister. As a young woman, she was addicted to prescription medication and crashed Derek's car while high. When she came home, she overdosed and was dead for three minutes. Derek saved her life, but was and still is angry with her. Amelia ended up sleeping with Derek's best friend Mark Sloan, following in the footsteps of her sister Nancy and her ex sister-in-law Addison Montgomery after making peace with Derek following his own shooting.
Amelia first appeared in season three, brought in because her boss was called for a consult on a comatose patient of Addison Montgomery's. Amelia came up with a plan, which was not approved by her boss, to wake the patient from her coma. The family of the patient urged her to perform the surgery which lead her to be fired from the original jobs he had. She soon begins to hang around Oceanside Wellness, annoying Addison a bit with her free-living attitude but also giving advice on Addison's relationship with Sam. Amelia was also the surgeon who operated on Dell after the car crash. As season 4 begins, Amelia is reluctant to visit her brother, Derek, when he is shot, but Addison eventually encourages her to go to Seattle to see him. On the way, Amelia has an in-flight romance with a man with a brain tumor and brings him to Seattle Grace for surgery. She and Derek bicker constantly over the surgery, but eventually settle their differences. She also has a one-night stand with Mark Sloan. When she returns to Los Angeles, she learns that there is a merger going on between the two practices. Amelia asks Naomi Bennett if she could become Ocean Wellness' new neurosurgeon, a move that annoys Addison.
When Charlotte is attacked and raped, Amelia is out with Cooper and Sam, but after receiving a visit from Violet, she comes to Charlotte's aid and confides in Charlotte about her addiction to prescription drugs and alcohol while stitching up a laceration on her arm. Later, when a drunken Cooper makes a move on Amelia, she rebuffs his advances and tells him to go home to his fiancée. Cooper eventually tells Charlotte about his interaction with Amelia and though Charlotte confronts her, they remain good friends. Charlotte asks Amelia to be her maid of honor in the episode "Something Old, Something New". At the wedding reception Amelia asks for a glass of ginger ale instead of champagne but by accident gets champagne, which she spits out. By the end of the season, however, Amelia relapses into addiction and refuses to get the help suggested by Charlotte. Charlotte tries to intervene with meetings, but Amelia skips them. Later, Charlotte discovers that Amelia operated on a patient while she was under the influence and as a result, Charlotte revokes all of her medical privileges.
Amelia continues her downward spiral in the premiere, injuring herself at a bar falling down drunk. Sheldon picks her up and takes her to the hospital where she sutures herself up in private to avoid Charlotte. The two later find out Pete has had a heart attack and needs surgery. Furthermore, Amelia operates on Pete's brain while under the influence. Later, Amelia passes a breathalizer test, but is seen drinking alone at home in Addison's old condo. Amelia's friend with Huntington's disease returns from Italy and requests Amelia's help with physician-assisted suicide. Pete and Sheldon disagree over Amelia's decision to help her. Later, Amelia and Pete discuss Pete's past when he reveals he once assisted a dying patient. Later Amelia begins a benzodiazepine injection on her friend, who has an adverse reaction and requests to be saved before she stops breathing; Amelia rushes her to the hospital, where Pete tends to her friend. Shortly after discovering her friend had completed her own suicide after being rescued, Amelia consumes what is believed to be three OxyContin pills she palmed after discovering the friend's body.
Following her friend's death, Amelia goes on a drug bender with a man she meets named Ryan. When she is caught by Addison doing drugs with Ryan, Addison kicks her out and they move into a hotel. Despite her friends' pleas to get help, Amelia begins writing prescriptions for herself until she is caught by Charlotte, who revokes her ability to write prescriptions. While high, Ryan proposes to Amelia and she accepts, giving him her father's watch. Soon after, Addison and the rest of the doctors stage an intervention for Amelia, but she resists until Addison discovers that she gave Ryan the watch. While telling the story, Amelia lashes out at her and leaves with Ryan. Later that night, Ryan dies from an accidental overdose. Eventually, Amelia is put into rehab, where she recovers from her addiction with the help of her co-workers at the practice, particularly Sheldon. In addition, Sheldon seems to display some romantic feelings towards Amelia, but she does not wish to pursue a romantic relationship.
Several weeks later after being confronted by Sheldon, Amelia admits that she is 20 weeks pregnant with her deceased fiancé's baby. At the moment, she is struggling on whether or not she should keep the baby and therefore, is heavily depending on Sheldon for advice. In the end she decides to keep the baby, but then she finds out her baby boy will be born with no brain, resulting in her shutting down emotionally and pushing her friends away. She eventually decides to continue the pregnancy to term and donate her baby's organs when he dies, after a father of a patient she pronounced brain dead decides to donate his daughter's organs so that something good can come from her death. In the season finale, she ultimately gives birth to her anencephalic son with the help of Addison and Jake. During her labor, she wishes to be left alone, fearing that if anyone was with her, she would break down and show her emotions. At one point while going through a painful contraction, she asks Jake to leave her alone, and when he refuses, she breaks down crying, letting all of her fears out in the open. Additionally while she is in labor, Jake finally tells the practice of her plans for organ donation which divides the doctors. Some believe it was a courageous act, while others believe it was murder. Sam is against the organ donation and refuses to do the harvesting, but after a talk with Amelia, he ultimately changes his mind. When it comes time for her to push, Addison hears her cries from outside the room and walks in. Amelia initially refuses Addison, but later allows Addie to coach her. When her son is born, she initially does not want to see nor hold him and wishes that his head be covered. Before taking him away for the donation, she decides to hold her baby, where she lifts the cap from his head. When the baby goes into respiratory distress in her arms, she momentarily breaks down, wishing for more time, but, then hands the baby over to Addison for the donation. Her last words to her son are "Your daddy is waiting for you in heaven. His name is Ryan."
Later on in the series, she gets engaged to Dr. James Peterson, an ER doctor at St. Ambrose Hospital, but breaks it off by moving to Seattle.
When Derek is offered a job by the President of the United States running a federal brain-mapping research project in Washington, D.C., Amelia, having begun assisting at Grey-Sloan Memorial Hospital with some of Derek's patients, takes over his practice, as the head of neurosurgery, at the hospital. She thus gained monikers, such as "Shepherdess" and "Lady Shepherd," so as to differentiate her from Derek. By season 11, she permanently moves in with her brother and her sister-in-law. Initially, she is known at Grey-Sloan largely as Derek's younger sister and once told her brother that she felt like she was constantly in his shadow. She soon begins a relationship with Owen Hunt (Kevin McKidd), her boss, and admits to Derek that she is falling in love with him. However, she later tells Owen that it was a mistake to mix their personal and professional lives. Following her brother's death and Meredith's "disappearance," she buries herself in work to distract herself. For some time she and Meredith were estranged over the circumstances of Derek's death but after listening to the very last phone message Derek had recorded for Meredith, she is finally able to let go of the animosity and reaches out to Meredith. Meredith's half sister Maggie moves in, with Amelia labeling the threesome "Lady Chief Trifecta." She gradually befriends Meredith's colleagues and is accepted into their circle. At the end of season 12, she marries Owen Hunt.
