Alex appears from the first episode of Grey’s Anatomy, having secured a position in the surgical residency program at Seattle Grace Hospital after graduating from the University of Iowa. He initially makes a poor impression on his fellow interns, and taunts Izzie Stevens (Katherine Heigl) when he discovers she used to be a lingerie model. After initial disagreements, Alex reveals to Izzie that his father was a heroin addict who used to beat his mother. He became a wrestler so he could defend his mother, and attended university on a wrestling scholarship. He and Izzie begin a friendship. At the end of the first season, George O’Malley (T.R. Knight) contracts syphilis from Alex through nurse Olivia Harper, causing animosity between the two.
In the show’s second season, Alex asks Izzie out in a date, but he is thrown by the news he has failed his medical board exams. Izzie is offended since he pays no attention to her during their date and so informs him that she no longer wants to go out with him. He later freezes during an emergency operation, needing George to take over from him. Alex’s relationship with Izzie is damaged when he experiences erectile dysfunction with her. He goes on to sleep with Olivia again, and when they are caught by Izzie, she breaks up with him. After retaking his exams, Alex manages a pass, and reunites with Izzie after a bomb scare in the hospital. They break up again, however, when Izzie falls for cardiothoracic patient Denny Duquette.
Alex spends a period of time working under neonatal surgeon Addison Montgomery (Kate Walsh), and though he is later released to work for plastic surgeon Mark Sloan (Eric Dane), he finds his interest returning to Addison’s firm. Addison is attracted to Alex, and the two share a kiss and later sleep together. However, Alex refutes her further advances.
In the aftermath of a ferry accident, Alex rescues a pregnant woman from beneath a fallen pylon. She awakes with amnesia, and grows close to Alex who helps her forge an identity for herself, picking out the name Ava. After she gives birth to her daughter, Ava’s memory eventually returns, although she tries to hide it from Alex as she had recently left a bad marriage. He convinces her to tell him her true identity, and she reveals herself to be Rebecca Pope. When Rebecca’s husband arrives at the hospital, she asks Alex to give her a reason to stay in Seattle. Alex turns her down, feeling that he is not good enough for her. Addison urges Alex to reconsider, but when he returns to the hospital, Rebecca has been discharged.
Rebecca returns in the show’s fourth season, and she and Alex sleep together before she goes back to her husband. Alex has a brief relationship with intern Lexie Grey (Chyler Leigh), but chooses to be with Rebecca when she returns and tells him she is pregnant. Izzie discovers that Rebecca is not in fact pregnant, and Alex cares for Rebecca when she becomes increasingly hysterical. After Rebecca slits her wrists, Izzie convinces Alex to admit her for psychiatric help. Alex discovers that Rebecca’s husband has left her and taken their child, and that she is mentally ill. Alex breaks down in Izzie’s arms, and the two kiss.
In the aftermath of Rebecca’s breakdown, Alex lashes out at Izzie, though they later go on to begin their relationship anew. Izzie begins hallucinating about Denny, and uncovers the fact she has metastatic melanoma (Stage IV) with an estimated chance of 5% survival. Alex is shocked by the news, but finds the strength to stay by her side. Izzie plans a wedding for their friends Meredith and Derek, but when Derek finds Izzie has another inoperable tumor in her brain, they give the wedding to Izzie and Alex, who marry in front of all their friends.
After their impromptu wedding, Izzie debates whether or not she should undergo a risky surgery to remove her tumor. Alex supports her, but eventually insists that she should have the surgery. Izzie agrees but signs a DNR form. Alex begs her to reconsider, but Izzie refuses and tells him that “if it comes down to it” he must let her go. After the surgery, Izzie loses her short-term memory and Alex works to help her regain it, which she does after an argument between the two. After they both realize that she has regained her memory, Alex apologizes for his earlier outburst, but Izzie’s heart rate flat-lines. The scene ends as Izzie’s friends and coworkers ignore the DNR order in an attempt to resuscitate her, and Alex looks on tearfully.
In the next season, Izzie regains a heartbeat. Both Izzie and Alex move out of Meredith’s house and into Derek’s trailer in the woods. But in a turn of events due to the failing economy, Seattle Grace has to make job cuts as they merge with “rival” hospital Mercy West. Fearing for her job, Izzie returns to work even though she is still undergoing treatment for her cancer. Izzie commits a grave mistake on a patient and gets fired. After being let go, Izzie disappears, leaving Alex a “Dear John” letter and no clue as to her whereabouts. Alex is currently trying to get back in touch with Izzie, but she is unreachable. When Izzie returns to the hospital, she and Alex speak in the gallery. She informs Alex that she could not forgive him for talking to the Chief. Alex says he could not forgive her either for leaving without talking to him first, and leaves her alone in the gallery.
When Meredith fears Alex will start sleeping around again to forget about his pain, she calls Izzie and tells her Alex might be moving on. At the same time, Alex has a one-night stand with Lexie. When Izzie arrives back home next morning, Alex almost immediately tells her he slept with someone else, but Izzie tells him they will get through this. When she later sees him with the results of her head scan earlier that day, they hug and Alex tells her he loves her so much, and that she made him a better guy – but being that better guy now, he finally understands he’s too good for this, he does not deserve to be treated like this, so he asks her to move on with her life, like he will; without each other.
Alex seems to have recently found that his calling is actually Peds and not Plastics as he had decided in the earlier seasons. Seeing Alex’s ability to handle child patients, Arizona Robbins shows an interest in mentoring him for that specialization. Initially, considering it to be a girls’ job, Alex does not want to consider it; however, he eventually develops a knack for it.
Alex’s brother Aaron comes to Seattle Grace for surgery, and lots of painful memories resurface because of this. Meredith discovers Alex, along with Aaron and their sister Amber, had been in foster care for 5 years when their mother could not take care of them. Alex has trouble adjusting to the fact that his brother is back, but they later make amends after the surgery, and Aaron thanks him for always protecting him from their father when he was young. That day, Alex is also served with divorce papers from Izzie.
In the first half of the 2-part season finale, Alex is shot in the hospital, but survives with the help of Lexie and Mark. While undergoing treatment, he mistakes Lexie for Izzie, telling her “[she] came back” and tearfully begging her never to leave him again; Lexie, declining to correct him, assures him that she never will.
In the opener of season 7, Lexie, unable to process the shooting, has a mental breakdown in front of Alex. Mark asks Alex to help her but he refuses and walks away. He returns to being very promiscuous and refuses to have the bullet from his chest removed, saying that it’s “his war wound.” After insulting Lexie, she cuts him down to size, stating that he is not “badass” for living because she is the reason that he survived and that while he was dying, he cried out for the wife who left him. Alex is left speechless.
Later, Dr. Bailey bars Alex from surgery until he has the bullet removed, which he later allows her to do. It is also revealed in the episode “Superfreak” that Karev is using the staircases because he is afraid of the elevators due to his shooting in the Season 6 finale. Chief Webber notices this and forces Alex to ride the elevator with him until he is no longer nervous inside it. Following the first few episodes of this season, Alex realises that his passions lie in Pediatric Surgery. He is further shown to be excellent with children, comforting with a young patient while growing her a new trachea.
He immediately gets on the wrong side of new Pediatric attending Stark, who then steals his idea for a infant liver transplant patient. Alex then attempts to sleep with virgin April Kepner in an on-call room but when April asks him to go a little slower, he blows up at her, telling her that he will not hold her hand and that he cannot take care of everyone. When Alex arrives to Cristina’s housewarming party, Jackson Avery beats him up brutally after a hysterical April tells him the story. Alex later confesses to Meredith he was in Iowa, and had gone home because his brother Aaron had been diagnosed with schizophrenia, discovered when Aaron had tried to kill his and Alex’s sixteen-year-old sister, Amber. Alex tells Meredith how he could not bear to stay with his family. Alex and Meredith perform an emergent surgery on a young boy by themselves during the night shift, dealing with the angry fallout from Stark (who would not answer his pager) but gaining the wordless approval of the Chief.
Alex is thrilled when Arizona returns from Africa and hopes she will come to work for the hospital again. When a shooter goes on a killing spree at a University nearby, patients are brought in, and Alex must operate with Stark on a young girl. When an infection in her leg threatens to shut down her entire body, Stark decides to cut off her leg. Arizona witnesses this, and after a desperate cry out from Alex, she begs the Chief to give her back her privileges, while Alex makes sure Stark does not touch the girl’s leg. Alex eventually gets over Izzie for good and falls for the new OBGYN attending, Lucy Fields, and she kisses him in episode 17. By the following episode, they seem to have started a relationship. When Alex is offered a job in Africa he tells Lucy but chooses to stay for her but when goes to tell her that he is staying she informs him that she took the job instead. Alex later finds out about Meredith sabotaging her Alzheimer’s clinical trial with Derek and rats her out which ends with him getting evicted by Meredith from her house. Later that episode, Alex is at Joe’s bar after losing a patient and Lucy walks in and asks him to make her stay. Partly drunk, he just tells her to “go to hell”.
Alex was at first hated by his fellow residents for ratting out Meredith, but (after Cristina almost killed him with a cc of epi) he later reconciled with them, apologizing to Meredith for putting her in the position she was in, she forgave him shortly after. While Catherine Avery brought the hospital’s residents for a special surgery, he “forfeited” after he was paged for Zola’s admittance for a bowel obstruction. Not able to keep it to himself (as Meredith and Derek knowing about it would jeopardize the adoption), Alex told Cristina who in turn told Meredith (and possibly Derek). While Arizona was irked by Alex’s actions, he still felt guilty for what he did to Meredith. While in surgery, Alex compared Zola to Sophia stating that Arizona had no parental rights (which caught her off guard). Later, the surgery was successful and relayed the news to Derek and a tearfully grateful Meredith.
Eventually, the hospital was required to transfer Zola to a different hospital as a result of a “conflict of interest”, but Alex, still feeling responsible for the adoption gone bad, worked feverishly to keep Zola at Seattle Grace. At the same time, he took the adoption case to a judge being treated for cancer, but the judge warned him that manipulating a judge was a felony. Eventually, Meredith and Derek got a court date regarding Zola, and a drunken Meredith kissed him on the cheek after a softball game, although she has no idea about what he did.