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Fans of Grey’s Anatomy still remember actress Katherine Heigl as Dr. Izzie Stevens on the medical drama. Now filming her upcoming Netflix series Firefly Lane, Heigl’s presence on the ABC show got a revival last season when her character was instrumental in the exit storyline of Justin Chambers, who portrayed her ex-husband Alex Karev.

The actress had several romantic storylines while on Grey’s during her almost six seasons on the show, including one with her on-and-offscreen bestie T.R. Knight. Portraying the lovable George O’Malley from 2005 to 2009, Knight left the show prior to Heigl’s departure but not before a love story unfolded for their two characters.

Katherine Heigl and T.R. Knight of ‘Grey’s Anatomy’ | Scott Garfield/Walt Disney Television via Getty Images

T.R. Knight’s exit from ‘Grey’s Anatomy

Knight’s tenure on Grey’s Anatomy was not without controversy. According to Entertainment Weekly, one on-set scuffle that quickly made headlines involved former co-star Isaiah Washington referring to Knight as a “f—-t” during argument with cast member Patrick Dempsey. Soon the melee was on the cover of tabloids and Knight was forced to publicly come out as gay. Washington was soon fired.

The former Grey’s star claimed that show runner Shonda Rhimes tried to discourage him from coming out. “I think she was concerned about having my statement come out so close to the [initial] event,” he told Entertainment Weekly in 2009.

Rhimes strongly denied the accusation. “I said, ‘If you want to come out, that’s awesome. We’ll totally support that,’” Rhimes recalled. “And then he went away, thought about it, and came back and said, ‘I’m going to make this statement.’ I remember saying to [fellow executive producer] Betsy Beers, ‘This is our proudest day here. T.R. got to come out, and I got to say to him that it wouldn’t affect his character.’” 

In Season 5, Knight seemed to get less airtime on Grey’s and was soon motivated to pursue other opportunities. “There just comes a time when it’s so clear that moving on is the best decision,” he said.

Izzie Stevens and George O’Malley go from besties to boyfriend/girlfriend

Playing best friends on Grey’s, Heigl and Knight’s characters took a different turn in Season 4. Though George was married to Dr. Callie Torres (Sara Ramirez) at the time, he and Izzie end up in bed together after he had a fight with his wife. The two tried to make their newfound romance work, but it eventually fizzled and they went back to friendship.

At first, Heigl was totally onboard with the coupling. “I was really excited about it in the beginning because, obviously, I got to work more with my best friend and that’s awesome,” she told Entertainment Weekly in 2010.

The romantic storyline never took off and the two characters parted as friends, with Izzie eventually ending up with Alex Karev.

T.R. Knight and Katherine Heigl of ‘Grey’s Anatomy’ | Ron Tom/Walt Disney Television via Getty Images

Katherine Heigl saw it wasn’t working

While enthusiastic at the beginning of the Izzie-George romantic storyline, Heigl soon saw that fans weren’t having it. “No, they did not like it,” she told Entertainment Weekly in 2010 soon after her departure from Grey’s.

Once the actress heard that the pair had earned a combined moniker, she got the hint that the coupling was a no-go.

“When I found out our little nickname was Gizzie, I knew it was over,” Heigl said with a laugh. “I was like, ‘We’re going to have to move on because that’s not hot. That’s not, like, Brangelina.’”

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As for Knight’s exit from Grey’s, it took time for Heigl to be on board with his choice to leave. “I didn’t think it was the right decision,” she said at the time. “I felt like some of the problems could be worked through. But by the time it came to fruition, I was [glad] for him because he was ready to go.”

While the Izzie-George pairing wasn’t beloved by Grey’s fans, the two characters are still held in high esteem by viewers.