Mal must choose which crew members to save when one is gravely wounded and two others are kidnapped. Simon finds an uneasy haven in a remote village, but River's uncanny perceptions jeopardize the Tams' temporary safety.
On arrival at the backwater colony of Jiangyin, Shepherd Book aids Mal and Jayne in unloading and penning the cattle. 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 to insult her and her beloved Serenity with his complaints about his predicament, and the Tams are left to their own devices. Simon quickly discovers River has wandered off.
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, and Simon 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 being more concerned for the effect Simon's paranoia may have on his rising career, his parents shrug his worries off as being overprotective of his little sister. Back in the present time, River follows Simon and his kidnappers, and is seized as well.
Mal and Zoe 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. He makes the unpopular decision to abandon the Tams in order to get Book off-planet and to proper medical treatment. As Simon consoles River about their imminent rescue, they see Serenity take off without them.
The doctor-less mountain 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.
On Serenity, Inara interrupts Mal and Wash's attempts to locate medical help to suggest an unpleasant alternative — asking an Alliance cruiser. Mal unhappily admits that they have no choice, and Serenity docks with the nearby Magellan. Mal explains their urgent need, but the Alliance officer callously dismisses Book's situation. When a weak Book manages to get the officer to check his identification card, however, the officer suddenly reverses himself and orders urgent care. Mal and the crew wonder what kind of connection with the Alliance Book must have, and when leaving on Serenity, a recovering Book dodges Mal's questions but acknowledges that "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. 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 superstitious woman there is only one explanation — that River is 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 Tam 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, revealing how he attained his position through the murder of his ailing predecessor. The patron quickly cuts her off with a slap, adding his own voice to the call for a witch-burning.
Simon appeals to the patron, fighting the torchbearers and chiding the villagers for their ignorance. When these efforts fail, he finally takes his place next to his sister, prepared to be burned with her. River announces that it's "time to go," and at that moment Serenity swoops over the village. As Jayne holds the villagers at gunpoint from Serenity's cargo bay, Mal and Zoe stride in and demand that the villagers release Simon and River; the village patron angrily declares that '[River] is a witch', leading Mal to pump a round into his shotgun and reply 'Yeah, but she's our witch.'
As Serenity leaves Jiangyin, Jayne hastily returns the valuables he had stolen from Simon during his brief absence. Simon asks Mal why he came back for them, and Mal explains off-handedly that it was because Simon was part of his crew. The Tams join the rest of the crew for a cheerful dinner, having found a home.