Hollywood changed forever in 1994 when ER made its premiere on NBC and transformed George Clooney from Working Actor You Might Recognize from Roseanne, The Facts of Life, and/or Return of the Killer Tomatoes! to, well, George Clooney. And though The Cloons hung up his scrubs in order to pursue big-screen opportunities in 1999, the long-running medical drama—created by novelist Michael Crichton—did just fine without Dr. Doug Ross.
The series ran for an impressive 15 seasons, racking up 124 Emmy nominations in the process. While it maintained an impressive roster of super talented series regulars (including William H. Macy and Ving Rhames) and guest stars (including Ewan McGregor and Susan Sarandon) and even managed to get Quentin Tarantino to direct an episode, ER also gave a jump start to the careers of dozens of then-newbie actors who would go on to rise up the Hollywood ladder.
1. Christina Hendricks
Three years after landing her first role with a four-episode arc on MTV’s Undressed, Christina Hendricks starred in four episodes of ER, as Dr. Abby Lockhart’s (Maura Tierney) neighbor with bad taste in men.
2. Matthew Settle
The object of Christina Hendricks’ affection? Matthew Settle, who’s best known as Rufus Humphrey, aka “The Dad,” on Gossip Girl.
3. Zac Efron
Not even one of those upbeat song-and-dance numbers from High School Musical could have changed the fate of Bobby Neville, the role Zac Efron played in ER’s 10th season (and his second-ever). He came in a gunshot victim and never went home.
4. Eva Mendes
Long before she and Ryan Gosling became parents in real life, Eva Mendes got practice by playing one on television. Her first credited role (we’re not counting her role in Will Smith’s “Miami” video) came in ER’s fourth season, when she spelled her name with an “z” instead of an “s.”
5. Nick Offerman
Before he was whittling things and keeping order in Pawnee, Nick Offerman played a badass rocker in ER’s fourth season premiere, which was also his television debut. Appearing in the same episode was future Oscar nominee John Hawkes (who, while not a household name yet, was certainly a veteran actor, having landed his first role in 1985).
6. Adam Scott
Offerman’s Parks and Recreation co-star Adam Scott also found an early paycheck on the set of ER during its first season, as a pedestrian who was hit by a car. “It was the first season of ER, so it was a pretty big,” Scott recalled to TVLine. “Everyone was discovering it, and George Clooney was on the cover of TV Guide as this new star. I was sitting outside waiting to work and he was playing basketball with a bunch of dudes. I remember just thinking, 'God, this dude is on the cover of TV Guide! He just looks like he doesn't care.’ If I was on the cover of a magazine, I’d be celebrating.”
7. Amy Ryan
In the same year she landed a starring role on the short-lived series The Naked Truth, and 12 years before she scored an Oscar nomination for Gone Baby Gone, Amy Ryan played a nun from a nearby Catholic school in the midst of a meningitis outbreak.
8. Emile Hirsch
Emile Hirsch made two appearances during ER’s sixth season as Chad Kottmeir, a teenaged alcoholic.
9. Chris Pine
Chris Pine’s ER gig didn’t require a whole lot of range—he played a drunk teenager recovering from a five-day bender of a Valentine’s Day party—but it did land him his first credited role.
10. Dakota Fanning
Dakota Fanning was just six years old when she made her onscreen debut as Delia Chandler, a little girl—and leukemia survivor—injured in a car accident who, it turns out, is not leukemia-free. Much of the episode revolves around Dr. Abby Lockhart’s (Maura Tierney) attempts to save Fanning’s life.
11. Shia LaBeouf
Before he was “not famous anymore,” Shia LaBeouf was not famous at all when he played Darnel Smith, a wheelchair-bound kid with muscular dystrophy, in a 2000 episode of ER.
12. Josh Radnor
After a couple of uncredited roles and the obligatory part on Law & Order, Josh Radnor played the syphilis-suffering gay lover of a Chicago alderman in ER’s ninth season. Two years later, he began filming How I Met Your Mother.
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13. Lucy Liu
Three years before her breakout role on Ally McBeal, Lucy Liu spent three episodes on ER as Mei-Sun Leow, the mother of a young boy with AIDS.
14. Aaron Paul
He may be just 35 years old, but Aaron Paul has gotten around with a series of one-off roles on shows like Beverly Hills, 90210, Melrose Place, 3rd Rock from the Sun, The X-Files, and NYPD Blue. In 2003, the future Golden Globe nominee added ER to his growing resume.
15. Josh Hutcherson
Josh Hutcherson was just 11 years old and already on his third professional gig in 2002, when he appeared in an episode titled “First Snowfall,” as part of a family run down by a drunk driver while building a snowman. Yes, a snowman.
16. Lake Bell
Lake Bell lucked out with her first credited role, which ended up being a two-episode deal during ER’s ninth season.
17. Wentworth Miller
Two years after making his on-screen debut in Buffy the Vampire Slayer, but five years before Prison Break made him a star, Wentworth Miller played Mike Palmieri, a high school wide receiver who got caught up in a football game riot.
18. Eric Stonestreet
A year after landing his first credited role on Dharma & Greg, Eric Stonestreet found himself in the ER—and on ER—after a failed attempt to give his ears a Spock-like makeover.
19. Octavia Spencer
Fourteen years before winning an Oscar for The Help, and just two years after beginning her professional career, Octavia Spencer appeared in a single 1998 episode of ER.
20. Anton Yelchin
Before he was starring in blockbusters like Star Trek, Anton Yelchin scored his first job—at the tender age of 11—as Robbie Edelstein, a kid who learns that his parents have been killed in a car accident.
21. Taraji P. Henson
More than a decade before she earned an Oscar nomination for The Curious Case of Benjamin Button, Taraji P. Henson impressed ER’s producers enough that they hired her for two episodes in 1998. As two different characters.
22. Jake Lloyd
Three years before he played Anakin Skywalker in The Phantom Menace, Jake Lloyd scored a four-episode run on ER (his first role) as Jimmy Sweet, the son of a prostitute.
23. Mena Suvari
Three years before she starred in American Pie and American Beauty, Mena Suvari played Laura-Lee Armitage, a reluctant teenage patient, in ER’s third season.
24. Gabrielle Union
In the same year that she starred in Bring It On, Gabrielle Union was beefing up her resume with an appearance on ER.
25. Kristin Davis
One month before moving into Melrose Place as the nutty Brooke Armstrong, Kristin Davis played the mom of an ER patient in 1995.
26. George Eads
Future CSI George Eads played paramedic Greg Powell in a few episodes between 1997 and 1998 (at the same time his future CSI co-star Jorja Fox played a doctor).
27. Janel Moloney
Four years before her star-making turn as Donna on The West Wing, Janel Moloney appeared in a 1995 episode, “The Birthday Party.” Her West Wing boss Bradley Whitford appeared in two episodes in the same year.
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All photos courtesy of Getty Images.