The show opens on the Tam estate, 11 years before the present day, where young Simon studiously addresses his homework. Little sister River, however, is more engaged in an imaginary battle against the Independents. Her Alliance forces, she declares, are sufficiently starved to have to "resort to cannibalism". A bemused Simon tries to steer River back to her dance practice, but she's not only completed this work, but points out a flaw in Simon's own textbook after a casual glance. Their father, Gabriel, enters, and the children assail him about obtaining a "dedicated sourcebox" (apparently the Firefly equivalent of an unrestricted Internet link). Gabriel forbids this, but acknowledges that their mother has already overridden him to order one — for Simon, at least. Tam Senior expects his son to become a "brilliant doctor" in return for this boon. Cut to the present-day brilliant doctor as he unsuccessfully tries to perform tests on his frightened and violent adult sister. Mal enters to complain about River's outbursts disturbing the cattle, their cargo for their current destination, Jiangyin. The captain makes it clear that they are to stay out of the way of the "trade to be done."

On Jiangyin, Shepherd Book aids Mal and Jayne in unloading and penning the cattle, while Zoë and Wash contemplate the practical advantages of smaller live cargo, like "black-market beagles". When River communes with the animals, Mal decides to send her and Simon off to town to stay out of the way of their "clandestine dealings". They join Inara and Kaylee as the women are shopping. Although Kaylee contemplates buying something nice for Simon, the doctor manages yet again to insult her and her beloved Serenity with his complaints about his predicament, and the Tams are left to their own devices.

Back at the impromptu cattle pen, Mal meets with his "disreputable" clients. Just as they come to an agreement on price, the local law enforcement arrives to arrest the clients, and in the ensuing gunfight, Book is grievously wounded. Meanwhile, River wanders into a country dance, where she quickly picks up the movements. Simon happily watches his sister enjoy herself for a change. River's ecstatic dancing suddenly falters when Book is shot, but before Simon can react to his sister's distress, he is kidnapped by a group of men. While he is dragged off, a flashback shows an adult Simon arguing with his parents that River is in trouble at the institute. Her letters, he insists, talk about events that never occurred as a code to ask for help, but his parents shrug his worries off as being overprotective of his little sister. They are more concerned about how such "paranoid" speculations might affect his swiftly advancing career. Back in the present time, River appears, as if they were playing hide-and-seek, and is seized as well.

Mal and Zoë manage to get Book back to Serenity to perform some field surgery to stabilize him. When Wash is unable to find the doctor to help Book, Mal realizes that Simon and River have probably been taken by hill folk who kidnap unwary people, especially skilled workers, to add to their numbers. He makes the unpopular decision to abandon the Tams in order to get Book off-planet and to proper medical treatment. Even as Simon consoles River about their imminent rescue, they see Serenity take off without them.

The doctor-less mountain village people welcome Simon and his sister, although he is less pleased with the situation. But when he sees the many ill villagers, he uneasily settles into his vocation. As he works, he tries to argue the inconsistency of this devoutly religious community kidnapping strangers to meet its needs, but Doralee, a village teacher, merely suggests that Simon may well be in the place he is fated to be. When Simon tells her, "this isn't our home," she replies, "If it isn't here, where is it?"

On Serenity, Inara interrupts Mal and Wash's attempts to locate medical help to suggest an unpleasant alternative — begging for help from an Alliance cruiser. When the Alliance personnel board their ship, an uncharacteristically deferential Mal explains their urgent need, but the Alliance officer callously dismisses their problem. When a weak Book manages to get the officer to check his ident-card, however, the officer suddenly decides to reverse himself and order urgent care. Mal, Zoë, and Jayne wonder what kind of connection with the Alliance Book must have. Later, when Serenity is departing, Mal asks the healing Shepherd about this. Book dodges the questions, but acknowledges "it's good to be home."

Back in the village on Jiangyin, Simon and River share a memory of their childhood, and River despairs of how her plight has taken everything Simon had away from him. Her brother responds, "Mei-mei, everything I have... is right here." When River tells Doralee about the cause of a young mute girl's silence, Doralee realizes that River has an unusual power. But for this religious woman, there could only be one explanation — River must be a witch.

Another flashback shows an embarrassed and furious Gabriel Tam retrieving his son from Alliance custody after an attempt to help River by meeting with someone in a "blackout zone." The elder Gabriel tells Simon that he will not protect his son from any further improprieties. Back in the present time, River's current impropriety has Doralee summoning the townspeople about the witch among them. The patron, or village elder, arrives to investigate. Unfortunately, River only seals her fate by reading him. As she tells of how the previous patron had been ill but was recovering when the current one visited him, the new patron quickly cuts her off by slapping her and adding his own voice to the call for a witch-burning.

Simon tries appealing to the patron, fighting the torchbearers, and chiding the villagers about "your lunacy, your ignorance." When these efforts fail, he finally takes his place next to his beloved sister, to be burned with her. River announces that it's "time to go," but it turns out that their departure is of a more earthly nature when Serenity arrives. As Jayne visibly aims a shotgun at the villagers, "big damn heroes" Mal and Zoë demand the release of their people.

As Serenity leaves Jiangyin, Simon asks Mal why he came back for them. "You're on my crew. Why're we still talkin' about this?" Mal shrugs. The Tams join the rest of the crew for a cheerful dinner. It appears that Simon and River have found a home.