In a scene shown later in the episode, after showering in the bathroom at the farm, Shane stares into the mirror at himself after shaving his head. As he wipes away the steam off the mirror, there's a look in his eye that says something about him has changed.
Earlier, Rick and Lori wait patiently at Carl's bedside for Shane and Otis to return from the FEMA command post at the high school, so that Hershel Greene can perform the surgery that will save their son’s life. Rick, weak from multiple blood transfusions to keep Carl alive, tells Lori a familiar story about a prank Shane pulled on the principal when they were in high school.
Focused on her son's health, Lori begs him to eat to keep his strength up, while Rick tries to convince her that Carl will be fine.
In the RV, Carol is crying over Sophia's disappearance in the bedroom, keeping Daryl bitter and awake. Andrea is still trying to put together a gun, this time using Daryl's and doing much better. He takes it back from her when he decides to go out looking for Sophia. With nothing else to do, Andrea decides to go with him. When Dale tries to object to them heading out in the middle of the night, Andrea shuts him down as she and Daryl head in to the woods.
Otis and Shane, still with a full head of hair, have made it in to the high school's auditorium and on to the bleachers, they determine that they still can't outrun the walkers as there are too many. When Shane spots a window and suggests they try to jump through, Otis rebukes him on account of his size. He instead tells Shane to go for the windows on his own while he draws the walkers away to the locker rooms - he says that the windows are larger and he can escape easily.
Otis' plan works, and he's able to draw most of the walkers from the auditorium, growling and reaching for him as they go, while Shane shoots at the dead from atop the bleachers. Shane makes it to the window and is almost out, but a walker makes it up the bleachers, grabbing for him through the broken window frame. He grabs his gun and shoots the walker, but loses his grip on the window and falls two stories below and lands hard on his ankle.
Glenn and T-Dog arrive at the farm and nervously discuss whether they're supposed to knock; they hadn't knocked on anyone's front door in months. But they're surprised by Maggie Greene, sitting in a darkened corner on the porch, listening in on their conversation. "Close the gate up the road when you drove in?" she asks, and Glenn sputters a yes. Maggie smiles and invites them inside, where they find Rick and Lori at Carl's bedside with Hershel.
Hershel states that Shane and Otis are taking too long to return and that Carl's condition is growing worse. He informs Rick and Lori that he may have to attempt the surgery without the equipment, and that they’re going to have to make a choice sooner rather than later. The two talk it over and Lori wonders if Carl might be better off dead, but Rick doesn't want to hear it.
He asks her what's changed since the CDC, when Jenner offered them a way out. Remembering how Jacqui committed suicide, Lori sobs, "Maybe this isn't a world for children anymore. We live with a knife at our throats every second of every day." She begs for him to give her a reason why it would be better to live.
But Rick still decides to fight for his son as Shane fights for his life at the school. Limping, Shane shoots various walkers but is about to be overrun when Otis saves him from the approaching walkers, though they both use their last rifle rounds. They start to limp away as the walkers tear at the fences.
Carl wakes for a very brief moment, and talks excitedly about the deer that he saw, but he then has a seizure. His pressure bottoms out and Rick desperately offers to do another transfusion. Hershel doesn't want to take any more blood from him in case he goes in to a coma or suffers cardiac arrest, but he begins to take out his kit anyway - it's the only way to keep Carl alive until Shane and Otis get back. "You're wastin' time," Rick says.
While they search the dark forest, Daryl tells Andrea about the time he was lost in the woods when he was a child. As they discuss Sophia's chances - he's hopeful, she's not - they come upon a Walker, hanging from a tree. His feet have been chewed at by walkers. He had committed suicide and left a note: "Got bit. Fever hit. World gone to shit. Might as well quit." Daryl scoffs, "Dumbass didn't know enough to shoot himself in the head." Daryl wants to leave it alone and not waste an arrow, but Andrea, disgusted, asks him to kill it. Daryl kills the walker in exchange for asking Andrea if she wants to live yet; she says she doesn't know if she has to live, wants to live, or if it's just a habit.
Unable to sleep, Carol joins Dale on the roof of the RV to help take watch. She can tell that Dale is worried about Andrea, and she tries to comfort him. But Dale leaves her alone on the roof, handing her a rifle she clearly doesn't know how to use.
At the farmhouse, Patricia is busy, stitching up T-Dog’s arm, while Glenn is trying to pray for the safety of Carl before Maggie interrupts him on the front porch. He's never prayed before, and he and Maggie discuss if God exists. Before she goes back inside to leave him alone, she tells him, "Feel free to believe in God, but you gotta make it okay somehow - no matter what happens."
As Carl sleeps, Rick returns to his conversation with Lori, having left it with her wondering if the world was worth living in anymore, and needing Rick to tell her something to hold on to. He says that Carl's reminisces about how beautiful the deer was when he woke up told him that there was still a world out there for them. But the latest transfusion wasn't enough, and Rick's hope is able to convince Lori to allow Hershel to do the surgery without the anesthetic. Patricia pulls the shade off a table lamp as Hershel sterilizes his equipment, and they place Carl on a metal trey. He's getting ready to start when the pick-up pulls in to the driveway, the headlights shining in through the window.
Shane has arrived with the supplies, but Otis isn't with him. Shane seems stunned, quiet. He tells them they were overrun, and that Otis didn't make it. Hershel demands that no one needs to tell Patricia until after the surgery, and Maggie sobs as Rick embraces Shane for bringing back the equipment and comforts him saying that Otis wanted to make it right.
Daryl and Andrea return safely to the RV, without Sophia. Carol sees and returns tearfully to bed, and Dale stops Andrea before she heads in for the night. He apologizes for making choices for her and gives back her gun, adding, "I can still ask. Please don't make me regret this."
"I'll take watch," Andrea tells him, and he asks if she forgives him. She stops before she climbs up the ladder on to the RV, and says, "I'm trying."
Glenn comforts Maggie over the loss of Otis, and she tells him about her stepmother and stepbrother, who both became walkers. Hershel is able to stabilize Carl, which leaves Rick and Lori near tears. Rick offers to help Hershel with informing Patricia about Otis. As she sobs, Shane looks on from the living room.
Shane goes to Carl's room, where he finds Lori at his bedside and stands back nervously. "Stay," she says to him, but he can't. Maggie finds him in the hallway and hands him some overalls. "I brought you some clothes. They won't fit well; they were Otis'."
Shane goes to the bathroom and has his shower, and with his full head of hair he finds a bald spot, where it looks as if hair has been pulled from his scalp. He remembers what happened at the high school as he looks around the bathroom in various drawers and cabinets for an electric razor.
In a flashback we see Otis pull Shane along after he collapses from his ankle injury. They shoot at various walkers and manage to get to the parking lot, a herd of walkers behind them. They are both down to their last round of ammunition. Shane tells Otis to leave him and take the supplies, but Otis refuses to leave him and pulls him up helping him.
Shane hobbles as the walkers descend on them. He looks at Otis. "I'm sorry," he says, and Otis looks at him, confused, as Shane shoots him in the leg with his last bullet.
Otis screams in pain, falling. Shane grabs for Otis' backpack with the supplies Carl needs inside, but Otis fights him, grabbing at a chunk of his hair and punching him, but Shane is able to overpower him, take the man's gun and get away.
The walkers descend on Otis, devouring him while Shane is able to hobble away unnoticed.
Back inside the Greene's bathroom, Shane shaves his head to hide the bald spot and protect his secret.
- Amber Chaney as Annette Greene (Photograph)
- Travis Charpentier as Shawn Greene (Photograph)
- Jewel Wilson as Josephine Greene (Photograph)
- Michael Koske as Callaway
- Michelle Flanagan-Helmeczy as Walker
- Charles Casey, Demetrice Jackson, Matthew Lyda, Eddie Rattanasouk, Jacque Tenpenny, Ashton Lee Woolen, Joe Hernandez, David Alexander, John Jaret, Ashe Johnson and Mark Teems as Walkers
- First appearence of Annette Greene. (Photograph)
- First appearence of Shawn Greene. (Photograph)
- Last appearance of Otis.
- This episode marks the final credited appearance of Pruitt Taylor Vince (Otis), after being killed off in the episode. Archive footage of his death in the episode was used in "Cherokee Rose".
- Shane becomes the first character in the TV Series to be responsible for the death of a living character (Otis).
- The title of this episode, "Save the Last One," references the well known rule in zombie apocalypse stories that survivors should always save the last bullet for themselves if surrounded by a group of zombies. This makes the title quite misleading, as Shane doesn't use his last bullet on himself, but on Otis. Similarly, the walker found hanging from the tree hanged himself instead of shooting himself in the head to commit suicide.
- When Daryl and Andrea found the walker hanging from a tree, his "poem" reads, "Got bit. Fever hit. World gone to shit. Might as well quit."
- The school used for filming the scenes was Newnan High School (NHS).
- Kevin Fitzpatrick, The Walking Dead 2.03 "Save the Last One" Comic-to-TV Comparison, (October 31, 2011).