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Izzie & Karev share a romantic moment on 'Grey's Anatomy.'

Let's Look Back On Izzie And Karev’s Grey's Anatomy Relationship

This explains why he did what he did to poor Jo.

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In Grey's Anatomy’s shocking March 5, 2019, episode, fans learned that Dr. Alex Karev left Grey Sloan Memorial Hospital to reunite with his ex, Dr. Izzie Stevens, and everyone basically lost it. Even years later, the show of Karev leaving is still felt among the fandom, especially since Izzie was written off the show back in 2010, so it felt kind of out of left field. To help you recall all that went down between them 10 years ago to lead to this plot twist, here's a timeline of Izzie and Karev's relationship on Grey's Anatomy.

Alex (Justin Chambers) and Izzie (Katherine Heigl) had an on-off relationship that was one of the staples of the first several seasons of Grey's. Granted, it seemed like nearly everyone hooked up with everyone at some point during their time at the hospital, but Karev and Izzie seemed to keep finding their way back toone another at different points of their medical journeys. So, although Izzie has been absent from the show for quite some time, it does make a bit of sense that Karev's departure had something to do with her. Although many fans were shocked by this ending for Karev, the history of his relationship with Izzie might bring back some of those warm fuzzies that made fans fall in love with the pair in the first place... and maybe even help them cope with Karev's unexpected decision and the toll it took on Jo Wilson (Camilla Luddington).

Season 1, Episode 1: They Meet As Interns

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Alex and Izzie both started out as interns at Seattle Grace Hospital together with Meredith Grey (Ellen Pompeo), Christina Yang (Sandra Oh), and George O'Malley (T. R. Knight).

Throughout Season 1: They Become Friends

Although Izzie wasn't thrilled when Karev revealed to her colleagues that she used to be a lingerie model, the pair later became pals. Alex revealed to Izzie details about his tough childhood, including the revelation that his father was addicted to heroin and used to abuse his mother. The pair grew close from there.

Season 2: They Start Dating

Alex and Izzie went on their first date in Season 2, but because Karev learned he failed his boards that day, he was off his game and upset Izzie by not kissing her. She was initially annoyed, but Karev later showed up at Joe's (the local bar) and kissed her passionately. They then started dating.

Season 2, Episode 10: Karev Cheats On Izzie

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Alex struggled to get intimate with Izzie and reverted to hooking up with nurse Olivia Harper. It wasn’t pretty.

Season 2: They Become Friends Again

Eventually, Izzie forgave Alex and got on friendly terms again. They rekindled their flame following a bomb scare in the hospital, and Karev realized he wanted Izzie back.

Season 2: Izzie Dates Denny

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Before Karev and Izzie could begin dating again, she instead fell for cardiothoracic patient Denny Duquette, and the two got engaged while Denny's heart deteriorated. When a transplant heart became available, Izzie cut Denny's LVAD wire to worsen his condition and move him up on the organ recipient register. Although the surgery was completed successfully, Denny died soon after (Season 2, Episode 27) from an unexpected stroke.

Seasons 3 & 4: They Date Other People

Following Denny's death, Izzie drunkenly hooked up with George O'Malley (who was married to Callie Torres). The pair initially tried to keep the hookup a secret, but eventually decided to tell Callie and begin a relationship with one another. It was short lived; they realized they lacked sexual chemistry and broke up.

Meanwhile, Karev became interested in a pregnant woman he rescued in the aftermath of a ferry incident. The woman initially awoke with amnesia from the incident, but eventually regained her memory and revealed herself to be someone named Rebecca Pope... and married. They slept together before Rebecca went back to her husband, and Karev briefly moved on to Lexie Grey, but he reunited with Rebecca again when she told him she was pregnant. Eventually, Izzie convinced Karev to admit Rebecca for psychiatric help following a suicide attempt, and Karev was single again.

Season 5: They Date Again

Alex and Izzie got back together in Season 5, but Izzie's persistent hallucinations of Denny made her realize something might be wrong. She discovered she had stage IV metastatic melanoma, which spread basically everywhere and gave her a 5% chance of survival. It was during this time that Izzie and Karev decided to freeze several embryos, just in case.

Season 5, Episode 22: They Get Married

While being treated for cancer, Izzie was planning Meredith and Derek's wedding. When Derek realized Izzie had a second brain tumor, the planned wedding ceremony was given to her and Karev instead, so they could get married before it was potentially too late.

Season 6, Episode 12: They Divorce

Izzie barely survived the cancer and returned to treat patients at Seattle Grace. However, when she accidentally administered an incorrect dosage to a patient in later episodes, she was fired. Thinking Karev was partially to blame for her firing, she wrote him a letter and left. Eventually, she came back for a final PET scan and showed Karev the clear results. However, Karev realized he wanted someone who would stick around for him, and the pair went their separate ways. She left without telling anyone where she went, but sent Karev signed divorce papers to end their marriage. That 2010 episode marked her last appearance on the show.

Season 16, Episode 16: Karev Reunites With Izzie

Ten years after Izzie left screens, her character returned to help wrap up Karev's storylines in Season 16. Fans learned through a series of self-narrated letters that Karev had reunited with Izzie, who had apparently used the embryos they froze when she had cancer and birthed two of Karev's children. When Karev discovered he had kids, he decided to move to be with them and Izzie, leaving his new wife Jo in the process.

Season 17 & Beyond: Jo Moves On

Even though Karev got to have his happy ending with Izzie, he still left a bit of a mess behind in Seattle. Not only did Jo have to deal with the end of her marriage, but she also had to deal with the fact that Karev left her without even saying goodbye in person. Jo’s way of confronting it was to… avoid it all, basically. After her marriage ended, Jo started hooking up with Jackson Avery. But a different type of relationship soon took precedence in Jo’s life. She became very attached to an infant named Luna whose mother died at Grey Sloan Memorial. Jo realized that she wanted to adopt Luna and become a mom. She also realized that surgery was no longer making her happy, so she switched specialties to obstetrics and gynecology. So yeah, Karev got a new beginning with Izzie when he left Jo, but Jo also got a new beginning of her own.

Karev and Izzie’s love story came full-circle as they went from bickering interns to surgeons with a family of their own. As is usually the case on Grey’s Anatomy, there was a whole lot of drama and a few other relationships along the way that got them to that point. But, in the end, Karev and Izzie became one more Grey’s Anatomy love story for the books.

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