The series, which premieres its 23rd season on Oct. 15, 2026, originally starred Ellen Pompeo, Sandra Oh, Katherine Heigl, Patrick Dempsey and more

Grey’s Anatomy was a hit on arrival.

Shonda Rhimes’s medical drama premiered in March 2005 to sky-high ratings, leading its time slot with a 7.2-million viewership gap from the rest of the competition. Ellen Pompeo, Sandra Oh, Katherine Heigl, Justin Chambers and T. R. Knight joined Seattle Grace Hospital as the intern cohort affectionately known as M.A.G.I.C. — Meredith Grey, Alex Karev, George O’Malley, Izzie Stevens and Cristina Yang — and Chandra Wilson, Patrick Dempsey, James Pickens Jr. and Isaiah Washington rounded out the eccentric hospital staff.

“What I remember about those first days was sort of knowing that we all felt like we didn’t know what we were doing, and that was exactly what we were playing,” Pompeo said in a 2025 interview with Shondaland. “I thought, ‘Well, this is either going to work, or it isn’t, but we truly don’t really know what we’re doing. We’re playing a bunch of interns who don’t really know what we’re doing.’ So, I knew I felt comfortable in our ability, and we were having a lot of fun.”

The series is notorious for its shocking plot twists (many of which bring dramatic, fatal ends to important characters). Heading into its 23rd season, which premieres on Oct. 15, 2026, Grey’s and its emotional storylines continue to have fans invested in the cast, both new and old.

Ahead of season 23, see photos of the show’s original cast from their early days.

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Ellen Pompeo as Meredith Grey

Pompeo led the show as the titular “Grey” — and continues to play her iconic role over two decades later (though she’s scaled back a bit since 2022).

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Sandra Oh as Cristina Yang

Oh received critical acclaim for her portrayal of the ambitious Cristina Yang from seasons 1 to 10.

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Patrick Dempsey as Derek Shepherd

Dempsey charmed Meredith (and the fans) as Derek Shepherd, famously known as McDreamy, from seasons 1 to 11.

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Justin Chambers as Alex Karev

Fans had a love/hate relationship with Chambers as the blunt (but soft on the inside) Alex Karev, whom he portrayed for 16 seasons.

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Katherine Heigl as Izzie Stevens

Heigl, a rom-com queen in Knocked Up and 27 Dresses, donned scrubs to play Izzie Stevens from seasons 1 to 6.

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Chandra Wilson as Miranda Bailey

Wilson made Miranda Bailey one of the most feared residents at the hospital and one of the most recognized in the fandom.

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T. R. Knight as George O’Malley

Knight’s George O’Malley experienced many highs and lows throughout his five seasons, which culminated in the character’s untimely death.

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James Pickens Jr. as Richard Webber

Pickens Jr. still plays the hospital’s father figure and mentor Dr. Webber.

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Isaiah Washington as Preston Burke

Washington’s run as attending surgeon Preston Burke was cut short by a controversial exit in season 3.

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Kate Walsh as Addison Montgomery

No one could forget when Kate Walsh’s Addison Montgomery entered at the end of season 1, shook Meredith’s hand and said, “And you must be the woman who’s been screwing my husband.”

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MerDer Forever

Meredith and Derek’s tumultuous relationship had viewers hooked from the beginning.

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All Together Now

Grey’s Anatomy has become the longest-running medical drama in history, with 466 episodes and counting — and it’s all thanks to fans’ love for the cast from the start.

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Award-Winning Smile

For season 1, Oh won Best Supporting Actress in a Series at the 2006 Golden Globes and Outstanding Performance by a Female Actor in a Drama Series at the SAG Awards.

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