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Izzie & Karev’s Relationship Timeline On 'Grey's Anatomy' Helps Clear Things Up

Dr. Alex Karev made his final appearance on Grey's Anatomy in 2019, but that didn't mean his character was completely out of the picture. In the shocking March 5 episode, fans learned Karev left Grey Sloan Memorial Hospital to reunite with his ex Dr. Izzie Stevens, and everyone basically lost it. Izzie was written off the show back in 2010, so fans might not remember the love story that led up to this final plot twist. To help you recall all that went down between them 10 years ago, 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 to one 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.

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, they pair later became pals. Alex revealed to Izzie details about his tough childhood; his father was a heroine addict and used to abuse his mother. The pair grew close.

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 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.

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 soon after died (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 decide to tell Callie and begin a relationship. 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

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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

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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. She accidentally administered an incorrect dosage to a patient in later episodes however, and 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

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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.

Now, Karev and Izzie's love story has come full-circle, and the once-interns are now established surgeons with children, and just like that, another original Grey's character is gone.