The group heads to Fort Benning, but are blocked by a pileup of abandoned vehicles on the interstate, and are delayed when the RV blows a radiator hose. A depressed Andrea expresses resentment towards Dale for saving her from the CDC explosion, while Shane decides to leave the group when he has the chance. The group narrowly avoids a herd of walkers passing through, but Sophia is discovered and chased into the woods. Rick distracts and kills her pursuing walkers, but she goes missing in the process. During a search party for Sophia, the group stops to search a rural church, at which point Andrea privately asks Shane if she can join him when he leaves the group. As the search continues, Rick, Shane and Carl discover a young buck; as Carl approaches the animal a gunshot from an unseen person strikes them both.

In a flashback to a time before the apocalypse, Shane tells Lori that Rick has been wounded from a highway shootout, and Lori in turn tells Carl. In the present, Carl has been accidentally shot by a hunter named Otis. Otis leads Rick, Shane and Carl to the home of veterinarian Hershel Greene, who manages to remove one of six fragments of the bullet. Hershel's daughter, Maggie, is sent to the group searching for Sophia and brings Lori to the Greene home to be with Carl and Rick. Rick gives blood to Carl while Otis and Shane go to the former FEMA aid station at a walker-infested high school to gather medical supplies. Dale and T-Dog wait at the RV; Dale fears that T-Dog may have contracted an infection from his injury, and the two search for antibiotics. Shane and Otis find the necessary supplies from the FEMA aid station, however they are forced to lock themselves inside the school after walkers surround them.

Hershel tells Lori and Rick that he might need perform Carl's surgery without anesthesia if Shane and Otis do not return soon. Daryl and Andrea return to the forest to find Sophia. The search leads to Daryl share a particularly telling childhood memory. In the woods, the two come upon a walker hanging from a tree, which they euthanize after a friendly debate. Glenn and T-Dog arrive at the Greene home, where T-Dog's injury is treated while Glenn and Maggie talk about faith. Lori contemplates letting Carl die to end his suffering, while Rick holds to the belief that Carl may yet live in a better future. Meanwhile, Shane and Otis fight to escape the high school, only to face more walkers at every turn. An injured Shane betrays Otis to escape the walkers, and returns to the Greene home just in time for Carl's surgery. Shane misleads everyone about Otis's death and destroys the only clue that he himself was responsible.

Dale, Daryl, Andrea and Carol arrive at the Greene home and set up camp as Carl recovers. Since Shane is still injured and Rick is weak from blood loss, Daryl decides to search alone for Sophia. He does not find Sophia, but instead finds a Cherokee rose (a Native American sign in which children were protected), and gives it to Carol. Hershel takes Rick on a tour; he then tells him that he should leave the property after Carl heals. Rick begs Hershel to reconsider that they leave; the latter will think about letting them stay if they follow certain guidelines. Dale and T-Dog decide to retrieve water from a nearby well, although they realize that there is a walker inside. Since the survivors cannot kill it for it might infect the water further, they decide to use Glenn as bait to lure the walker out of the well. They succeed, but due to the moisture from the well, the walker's legs and internal organs spill back in the well, infecting the water; T-Dog then kills the walker. Maggie and Glenn decide to head to a local pharmacy, where Maggie offers to have sex with Glenn. Glenn retrieves a pregnancy test, requested by Lori; Lori uses it and realizes that she is pregnant.