In the spring of 2005, ABC was on quite an upswing. Teri Hatcher was getting desperate on Wisteria Lane, while Matthew Fox was wondering just what kind of island he crash landed on, putting the floundering network back on the map culturally when their shows began the fall before. And then along came Ellen Pompeo

On March 27, Grey's Anatomy, a medical drama series from first time showrunner Shonda Rhimes, debuted as a midseason replacement for Boston Legal, introducing the world to Meredith Grey, McDreamy, Seattle Grace Hospital, and one particularly important Snow Patrol song. For 14 seasons, hopelessly devoted fans have kept the show alive, long after both Desperate Housewives and Lost (as well as countless other shows that came after them) got the ax. 

But the funny thing about the road to 300 episodes is that it's hardly ever paved smoothly. No, as Grey's as trudged on to join a club very few other shows have, it's faced its fair share of turmoil, from dramatic cast departures and one heck of a fallow creative period—and yet it still managed to not only survive, but thrive as one of TV's most prolific shows.

Grey's Anatomy, Patrick Dempsey, Ellen Pompeo


Initially intended to receive only a four-week run as James Spader and William Shatner took a break from their Beantown courtroom shenanigans, the ratings momentum seen by Grey's (which was averaging 17 million total viewers a week, a solid 5 million more than Boston Legal) was enough to convince ABC to risk the ire of David E. Kelley by bumping his show off the schedule until the fall in favor of fostering audience development on the sexy new show. By the time Kate Walsh showed up in the first season finale to deliver Addison Montgomery's infamous "And you must be the woman who's screwing my husband" line, Pompeo and her co-stars Patrick Dempsey, Katherine Heigl, Justin Chambers, T.R. Knight, Sandra Oh, Isaiah Washington, Chandra Wilson and James Pickens Jr. were well on their way to becoming household names.

However successful that first run of nine episodes was, it would prove to be nothing compared to the way the show absolutely exploded into the upper echelon of pop culture when ABC wisely decided to air it behind Super Bowl XL the following season. The episode, the first of a two-part story that featured high-profile guest stars Christina Ricci and Kyle Chandler and ended with Meredith's hand around an active bomb, would become the show's highest-rated episode ever with 37.88 million viewers.

Jeffrey Dean Morgan, Katherine Heigl, Grey's Anatomy


As new fans brought in thanks to the Super Bowl bump stuck around to watch Heigl's Izzie fall in doomed love with the terminally ill Denny Duquette (guest star Jeffrey Dean Morgan), culminating in an unforgettable season finale featuring that aforementioned Snow Patrol song, a cultural phenomenon was born. One that gave ABC the courage to move Grey's away from its perch at Sundays at 10 p.m., behind its solid Desperate Housewives lead-in, to Thursdays at 9 p.m., building a night of female-skewing dramas, including Ugly Betty at 8 p.m. and the rotating stable of flops at 10 p.m., around it. And while the show ranked as the No. 9 series on TV in season three, the cracks were starting to show.

The behind-the-scenes drama began when tabloids caught wind of an on-set skirmish between Washington and Dempsey that resulted in the former referring to their co-star Knight as a gay slur, prompting the previously closeted actor to come out of the closet. All would seem to have been smoothed over by Washington's public apology for his "unfortunate use of words during the recent incident on-set," however, by the time the Golden Globes rolled around in early 2007, he reignited the controversy by tarnishing their Best Drama win as he hijacked the cast's moment with reporters backstage to state, "No, I did not call T.R. a f----t." While Heigl was winning the show its first Emmy and Walsh was getting her very own spin-off, Washington was seeing his contract terminated with haste. And the reverberations would be felt for seasons.

By the time Knight was asking to be let out of his contract in season five, he was openly admitting to a breakdown in communication with Rhimes that he felt began after the Washington incident and contributed to his much-diminished screen time. Concurrently, Heigl, riding high on the success of Knocked Up and probably feeling a little protective of her BFF Knight, was picking her own fights with Rhimes, calling Izzie's affair with George in season four a "ratings ploy" in Vanity Fair and refusing to submit herself for Emmy consideration the year after her win. "I did not feel that I was given the material this season to warrant an Emmy nomination and in an effort to maintain the integrity of the academy organization, I withdrew my name from contention," she said in a statement that did her no favors with just about anyone.

Although, she may have been on to something. After reaching stratospheric heights, Rhimes and her writers seemed to falter. Characters were saddled with ridiculous plotlines (Izzie's "ghost sex" with Denny in season five, a symptom of her undiagnosed tumor, comes readily to mind, as well as the merging with rival hospital Mercy West, which brought in an influx of new faces, not all of them well-received), a well-intentioned, but ill-advised musical episode happened in season seven, and a general malaise was apparent. The show was never bad, per se—there was almost always at least one thing in even the worst of episodes that was worth the price of admission—but it was certainly on its way to becoming inconsequential.

Grey's Anatomy, Ellen Pompeo, Sandra Oh

ABC/Eric McCandless

And then something remarkable happened just before the beginning of the tenth season. OG star Oh, who'd spent the last nine seasons as Mer's delightfully prickly person Cristina Yang, announced that she'd be taking her leave at the end of the season. While she certainly wasn't the first original cast member to leave—not to mention the sort of revolving door process that had begun with most new cast additions—this was perhaps the first exit that was allowed to happen on its own terms, allowed to play out over the course of the season. And in doing so, the show's focus suddenly snapped back into view.

While myriad other stories of course continued around her, the conclusion of Cristina's love story with Mer gave the two main characters a purpose that they'd been lacking as they'd sort of stabilized in the later seasons. Suddenly, the show felt fresh again.

Following Oh's exit, which fans had a season to steel themselves for, came the shocking departure from McDreamy himself when Dempsey was released early from his newly extended contract and Derek Shepherd was tragically killed off. While the death certainly rubbed some fans the wrong way (though, as Rhimes argued in the aftermath, any other departure would've been a total betrayal of the love story we'd been asked to invest in for the past 11 years), it only further reinvigorated Meredith's story. We were suddenly watching something we'd really never seen before: A woman beginning the second act of her life, after tuning in every step of the way for her first act.

Like Law & Order: SVU—another prolific show in the 300 episode club—and its continued central focus on Mariska Hargitay's Olivia Benson, the outside forces of cast upheaval have had the positive side effect of ensuring that Meredith's story still feels fresh all these years later.

When the 300th episode debuts tonight, Grey's Anatomy won't look much like it did the day it premiered. Only four of its original cast members will be around, the set's underdone a face lift—hell, the hospital is even on its third name! Will it ever be able to return to the heights of its halcyon days? Probably not. But it's weathered every storm its ever crossed paths with. It's endured. And with Meredith front and center, it'll always feel like Grey's.

Grey's Anatomy airs Thursdays at 8 p.m. on ABC.

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