Episode: "The Time Warp" For years, we'd heard about the legendary Ellis Grey, who won the Harper Avery twice and created the laprascopic Grey method, but it wasn't until Paulson takes on the role in the 1982-set flashback episode "The Time Warp" do we get to see Meredith's mother in all her glory as she and Richard, outcasts for their gender and race, respectively, diagnose a patient with GRID (a precursor to AIDS).

Episodes: "It's the End of the World" and "As We Know It" Ricci's Hannah has the misfortune of being the girl with her hand on a bomb — before Meredith is. To stop a patient from bleeding out, she places her hand inside him, not knowing that he had a homemade bazooka shot into his body. Unable to move as the bomb squad strategizes, Hannah has a breakdown and runs out, leaving Meredith to take her place.

Episodes: "It's the End of the World" and "As We Know It" The Friday Night Lights alum plays a tough-as-nails bomb squad leader who helps evacuate the hospital when a man comes in with a live explosive in his gut. The sometimes-brash Dylan helps Meredith stay calm after she's forced to put her hand inside the man to stabilize the bomb. But after she hands the bomb off to Dylan, he's blown to bits (pink mist) right in front of her. He later appears in Season 3 when Meredith drowns, coaching her in the afterlife to return to the living.

Episode: "Owner of a Lonely Heart" Arquette's Constance Ferguson is a loudmouth prisoner who decides to swallow four razor blades to get out solitary confinement. Unfortunately for her, the uncompromising, unsympathetic Cristina Yang is her doctor, which leads her to swallow a broken light bulb in order to remain in the hospital. Yang senses her sheer desperation and relents, granting her an extended stay at Seattle Grace.

Episode: "Walk on Water" Nearly unrecognizable, Reaser makes her first appearance as the disfigured Jane Doe in the first of three episodes about a ferry boat crash that claims many lives — including, at least temporarily, Meredith's. As Dr. Sloan reconstructs her face, Dr. Karev indulges her nascent crush. She rechristens herself Ava, before discovering that she is actually the very married Rebecca Pope. She later leaves her husband and child for Karev, but when their relationship goes south, she slits her wrists and lands in a mental ward.

Episodes: "Crash Into Me Part 1" and "Crash Into Me Part 2" Green appears as Nick Hanscrom, a patient who has a tumor removed from his neck, leaving just a thin layer of skin covering his artery. After a little flirting with Lexie, he nearly scores a date with her, but a too-hearty laugh busts his artery, sending a shocking spray of blood all over the place. He later dies from his injury, leaving Lexie devastated.

Episodes: "These Ties That Bind," "All By Myself" and "Beat Your Heart Out" After the abrupt departure of Erica Hahn, the Chief begins grooming Dr. Dixon (McDonnell) to be the next head of cardiology, much to Yang's chagrin. Dixon has Asperger's syndrome, making communication with her difficult. Eventually, she, like Hahn, faded into oblivion.

Episodes: "Wish You Were Here", "Sympathy for the Devil" and "Stairway to Heaven" Five days before his execution, death row inmate William Dunn is brought to Seattle Grace after being stabbed in the spine with a shank. He spends his time there trying to convince Meredith to let him die — and donate his organs — but Derek and Bailey decide not to go through with it during surgery. Meredith later attends his execution upon his request for a friendly face in the room.

Episode: "Shiny Happy People" In a surprising turn for a Disney star, Lovato plays a suspected schizophrenic who tries to claw her own eyes out and stab herself in the heart with a syringe. Suspecting there could be something else wrong, Alex runs extensive tests that lead to the real culprit: She has a small hole in her inner ear, which amplifies sound, causing her great pain. She wasn't crazy after all.

Episodes: "Sympathy for the Parents," "How Insensitive," "Sanctuary" and "Death and All His Friends" After his wife is taken off life support at Seattle Grace, Gary Clark (O'Neill) blames Derek, Lexie and Webber for his wife's death. In a fit of rage, he returns to the hospital planning to kill the three of them and any other doctors who get in his way — including Reed and Dr. Percy. After shooting Alex, Owen and Derek — and nearly killing Lexie — he uses his last bullet to commit suicide.

Episodes: "Sanctuary," "Death and All His Friends," "These Arms of Mine" and "That's Me Trying" Mary Portman (Moore) is a tragic case of wrong place, wrong time. She comes to Seattle Grace for a colostomy reversal — on the same day that Gary Clark rampages through the hospital. After Clark shoots Dr. Percy in her bathroom, Mary helps Bailey try to save him, but to no avail. When Mary returns to the hospital six months later for the surgery, she never wakes up and is eventually taken off life support.

Episode: "Into You Like a Train" Bonnie Crasnoff (Keena) is admitted to Seattle Grace after a horrific train crash in which she and another passenger are impaled by the same metal pole. In order to save the other passenger, whose injuries are slightly less severe, they decide to move Bonnie off the pole, knowing she likely won't survive. She dies, but reappears in Season 3 during Meredith's vision of the afterlife.

Episode: "No Good at Saying Sorry (One More Chance)" Robbie Stevens (Lawrence) isn't the best mother to Izzie. She spends all her money on psychics, forcing Izzie to get a job as a lingerie model to pay for medical school. When she visits Izzie while she's undergoing treatment for cancer, Izzie and Bailey conspire to lie about Izzie's prognosis so that Robbie will leave Seattle.

Episodes: "Crash Into Me Part 1" and "Crash Into Me Part 2" Harold plays a paramedic whose partner suffers a seizure while driving their rig, causing them to crash. He suffers internal injuries, but refuses treatment because, it's discovered later, he's a white supremacist with a swastika tattoo on his stomach. Nevertheless, Bailey skips lunch with her estranged husband to complete the surgery. It's the end of her marriage, but she gets her revenge when sewing Shane up, destroying his swastika in the process.

Episodes: "Where the Wild Things Are" and "Piece of My Heart" During a camping trip, newly married Phillip Robinson (O'Mara) recklessly decides to touch a bear cub, causing its mother to attack him, his brother and his new wife Jennifer (DuVall). It turns out, Phillip has a brain tumor that causes him to make impulsive decisions. (He did marry his rebound girl, afterall.) After his brother dies, Phillip is inducted into Meredith and Derek's brain tumor trial, though he dies on the table.

Episodes: "Six Days (Part 1)" and "Six Days (Part 2)" The Parenthood star plays Heather Douglas, a patient with a severe case of VATER syndrome, which forces her to walk at a 90-degree angle. Izzie becomes emotionally attached to Heather, pushing for Derek and Callie to do a surgery that would help her stand up straight. When it turns out that her insurance company won't pay for the surgery, Izzie uses part of her $8.7 million inheritance from Denny to pay for it herself.

Episodes: "Dream a Little Dream of Me (Part 1)" and "Dream a Little Dream of Me (Part 2)" After getting into a major car accident with her two friends and their husbands, Sarabeth (Peters) learns that not only was her husband fired from his job eight months ago, but he's also cheating on her with her friend. When Bailey finds out that their insurance expires at midnight, Bailey turns back the clock so Sarabeth's husband's surgery is covered.

Episodes: "Crash Into Me Part 1" and "Crash Into Me Part 2" The Sons of Anarchy star portrays Stan, a paramedic who is crushed from the waist down when another rig crashes into his. Despite his gruesome injuries, he yells out for the rescue workers and doctors to stop trying to pry open the ambulance because an oxygen regulator is embedded in his partner Ray's back, which caused a tear in his heart. He saves Ray's life before dying.

Episode: "Great Expectations" Before the Amish were all the rage on TV, Boston and 90210's Stroup play Rachel and Jilly, two Amish girls who ran away from home when they were 16, the latter of whom has Stage 4 cervical cancer. Rachel calls Jilly's Amish parents, knowing that since Jilly wasn't baptized when they ran away, she can still return to the community and die where she was born. Rachel, on the other hand, is shunned forever.

Episode: "Here's to Future Days" The Friday Night Lights alum plays a soldier with a mysterious pain in his leg. He asks the doctors to amputate and fit him with a prosthetic so he can return to duty. After much protest, the docs go through with it. Charlie becomes the inspiration for George to join the army, which leads to him heroically jumping in front of a bus to save a woman before he was scheduled to ship out.