10 Biggest Plot Twists in Grey’s Anatomy’s 21-Season Run, Ranked

When it comes to hard-hitting medical dramas, Grey’s Anatomy stands proudly at the forefront of this genre. For 21 seasons, this drama has delighted fans with its unique ensemble of lovable characters, intense plotlines, and tear-jerking episodes. As such, many long-term fans of the show feel as if they’ve been on an emotional rollercoaster, thanks to Grey’s Anatomy’s huge number of twists.

Even after so many years on air, Grey’s Anatomy still knows how to surprise its fans. Every season is fitted with another range of twists and turns, causing fans to wonder where the story will take them next. With episodes like “Flight” and “Now or Never” defining the series, Grey’s Anatomy just wouldn’t be the same without its plethora of plot twists.

10. Derek Has a Surprise Connection to Addison Montgomery

Season 1, Episode 2, “The First Cut is the Deepest”

The very first episode of Grey’s Anatomy introduces fans to a collection of fresh faces, including Meredith Grey and Derek Shepherd. From their first moment together, there’s an undeniable spark, and fans can sense that this relationship will blossom into something beautiful. However, in the next episode, “The First Cut is the Deepest,” the audience discovers that Derek is already married.

Although Derek’s relationship with Addison Montgomery is a tad rocky, to say the least, a lot of fans were completely shocked to hear that the charming surgeon was already taken. This is especially true considering that Meredith and Derek were set up as the perfect couple in the previous episode. Additionally, Derek’s introduction painted him as a kind, honest man, so fans were completely surprised to see him cheat on his wife. Though Grey’s fans know that he was meant to be with Meredith, it’d take a little while for them to get together.

9. An Old Face Returns to Seattle Grace

Season 6, Episode 26, “Sanctuary”

Gary Clark is an infamous character in Grey’s Anatomy history, but his introduction was quite sincere. Clark’s wife was taken to Seattle Grace for a surgical procedure, but she unfortunately suffered complications. A short while later, she had to be taken off life support, and Gary sued the hospital for malpractice. However, he took things too far in “Sanctuary” when he returned to the hospital with a gun and shot multiple characters.

Clark’s rampage was entirely unexpected for fans because he seemed to be quite a weak man whose bark was much bigger than his bite. After killing Reed Adamson, he then burst into the OR and shot Alex Karev and Derek Shepherd. This was a particularly shocking episode, and many fans cite it as Grey’s‘ best season finale. The nail-biting twist highlighted the intensity of gun violence in the US and how these tragedies can occur at any time and in any place.

8. Richard Uncovers a Family Secret

Season 11, Episode 4, “Only Mama Knows”

Richard Webber’s relationship with Ellis Grey was scandalous in itself, but adding Maggie Pierce into the mix only made things more dramatic. In “Only Mama Knows,” Webber discovers that Maggie is the daughter he conceived with Ellis, proving that their relationship was a lot more serious than fans first imagined. Surprisingly, Webber welcomed his daughter with open arms, which also helped to strengthen her bond with her half-sister Meredith.

Though some fans see Richard’s relationship with Maggie as a little far-fetched, a lot of audiences see it as a great way to bring certain characters together. There’s no denying that working at Seattle Grace is hard, but Maggie Pierce exemplifies that the doctors are like family and must stick together no matter what. Overall, Richard’s relationship with Maggie was pretty shocking at first, but it ultimately allowed fans to explore more of his past.

7. Cristina’s Relationship With Owen Turns Dangerous

Season 5, Episode 19, “Elevator Love Letter”

Cristina Yang and Owen Hunt’s relationship is a bit unexpected, and it wasn’t a smooth ride. In “Elevator Love Letter,” the pair are fast asleep in bed. Suddenly, Hunt starts having a traumatic nightmare, a symptom of his PTSD, and unconsciously wraps his hands around Cristina’s neck.

This scene was a raw depiction of some people’s real-life PTSD experience, but it served as something of a twist because fans see, for the first time, more severe symptoms of Owen’s ongoing PTSD. Cristina decides to support Owen through his PTSD, but the immediate aftermath of this action was devastating to watch.

6. Jo Gets a Surprise Visit at Work

Season 13, Episode 23, “True Colors”

Jo Wilson’s character means a lot to fans, mainly because her domestic violence arc was so relatable and powerful. After briefly mentioning the struggles she had with her husband, Paul Stadler, in the past, he unexpectedly turns up at the hospital in “True Colors.” Matthew Morrison did a fantastic job of bringing this manipulative and aggressive character to life, and fans can feel Jo’s terror when she first sees him.

The first time Jo sees Paul is in an elevator, a claustrophobic environment that only serves to heighten the episode’s tension. Not only can viewers relate to this distressing moment, but Paul’s appearance surprised viewers, as Jo had previously suggested Paul could “never find her.” Although Paul gets what he deserves a few episodes later, the initial shock of seeing him places “True Colors” at the halfway point on this list.

5. Arizona Was Unfaithful in Her Relationship With Callie

Season 9, Episode 23, “Readiness is All”

Cheating scandals are a big part of Grey’s Anatomy’s appeal, as they highlight how effectively the show can blend personal and professional problems. Yet, when Arizona cheated on Callie with Lauren Boswell in “Readiness is All,” fans were more than surprised. As such, this plotline is often viewed as more nonsencial than shocking.

Though Arizona and Lauren’s flirting seemed harmless at first, fans never expected them to actually sleep together. This upset a lot of audiences, mostly because they adored Arizona’s relationship with Callie and wanted them to make it work. Yet, her dalliance with Lauren proves that a lot of these professionals are only loyal to one thing, and that is their jobs.

4. Amelia Shepherd Receives a Tragic Diagnosis

Season 14, Episode 2, “Get Off on the Pain”

Devastating diagnoses are pretty common throughout Grey’s, but it’s always a bit more shocking when these bombshells affect one of the hospital’s own. In “Get Off on the Pain,” Amelia Shepherd discovers that she’s had a brain tumor for the last decade. Although Owen believes that she’s still struggling with PTSD after Derek’s death, an MRI reveals that she’s been living with quite a large tumor.

This episode is quite jarring because, at first, Amelia doesn’t know whose scans she’s looking at. In fact, she’s quite impressed by the tumor’s magnitude. Thus, Amelia’s diagnosis opens up a large can of worms and the audience is upset at the fact that this brilliant neurosurgeon will have to go through the same treatment she offers her patients on a daily basis.

3. Lexie Suffers a Tragic Accident

Season 8, Episode 24, “Flight”

The surgeons at Seattle Grace are often tasked with dealing with life-or-death situations, but “Flight” puts the crew in their own crisis and even places a few of their own in grave danger. As such, “Flight” instantly became one of Grey’s Anatomy‘s saddest episodes when the plane, which was taking six of the Seattle Grace surgeons to Boise, crashes. The episode included numerous shocking injuries. Aside from Mark suffering a cardiac tamponade, Lexie Grey dies after being crushed by debris.

Grey’s death was particularly shocking because many fans feel that her life ended so abruptly. Just halfway through the episode, fans had to face the fact that one of the show’s most beloved characters had passed away, and now the surgeons had to fend for themselves. Though this wasn’t the most shocking death in the show, and perhaps audiences predicted that Meredith, Cristina, Mark, and Derek would definitely survive, many fans weren’t ready to say goodbye to Lexie so quickly.

2. Fans Must Say Goodbye to Their Favorite Surgeon

Season 11, Episode 21, “How to Save a Life”

Derek Shepherd’s death brought tons of fans to tears, and the vast majority of viewers couldn’t actually believe he was gone. In “How to Save a Life,” Derek is involved in a terrible car accident and passes away shortly after Dillar Medical Center failed to give him a CT scan. Audiences are then forced to accept that one of Grey’s Anatomy’s most beloved characters will no longer be involved in the show.

Though he shows up again in Grey’s via flashbacks, the loss of Derek Shepherd impacted every character on the show. Meredith was never quite the same, and the team didn’t feel as unified as it used to be. Even though he passed away nearly 10 years ago, fans will never truly get over his loss.

1. A John Doe Patient Is Revealed

Season 5, Episode 24, “Now or Never”

Fans quickly fell in love with George O’Malley, the adorable intern who soon grew into an admirable surgeon. Throughout Season 5, O’Malley discussed joining the army as a trauma surgeon, which truly upset his peers. In “Now or Never,” a John Doe patient arrives at the hospital after jumping in front of a bus while trying to save a random citizen. It’s later revealed that this patient is actually George, and his body is disfigured beyond belief.

George O’Malley’s death was a crucial moment for fans because it signified the loss of the first MAGIC-era intern. He was terribly young and died saving another person’s life, showcasing his bravery in difficult situations. As soon as George traces “007” on Meredith’s palm, “Now or Never” becomes one of the most devastating episodes in Grey‘s history. His death rocked fans, and as one of the first major character deaths in Grey’s, the revelation that John Doe was George O’Malley was the biggest plot twist in the series.