The episode starts out with a flashback to River and Simon’s childhood and then goes back to present-day River who is having a mental breakdown. The crew of Serenity plans on selling off the cows they smuggled from the previous episode. Mal tells Simon and River to take a walk around the town away from the deal-making point. They go into a shop where Inara and Kaylee are looking around. Simon snaps at Kaylee about being out in a backwater planet, resentful of the lack of respect he’s getting. Kaylee chastises him for his words, but River wanders off before Simon could word out a proper apology.
From this point on, the episode follows two parallel plots: Simon and River getting to know the new planet and the rest of the crew of Serenity having to deal with the consequences of their latest attempt at smuggling going south.
River joins in on a local folk dance while Mal, Jayne, and Sheperd Book get caught in the crosshairs of local law enforcement who arrest the buyers. The music from the dance eventually crosses over with the gunfight that ensues. (It’s a space western, just go with it.) Shepherd gets shot and finds himself in critical condition. Meanwhile, Simon and River kidnapped by settlers and think that Mal has abandoned them, not realizing that Shepard Book was critically injured.
The crew of the Serenity debates over where they could get a doctor without Simon, realizing that they have no choice but to ask the Alliance for help. The Alliance men check in and take Book to the infirmary. They later learn that Book has some kind of past with the Alliance. Jayne says that life without Simon and River on board could be a lot simpler.
Simon and River are taken to a small village of settlers in need of a doctor. Simon gets straight to work and the two of them try to make the best of the situation. River later reveals some information to the local teacher about a patient in the clinic who has been mute for two years. Unfortunately, she also gave away the fact that she could read minds. The nurse thinks that River is a witch and it eventually leads to village planning on burning her at the stake. (Seriously? Backwater town with religious beliefs that sets on burning an innocent girl? How cliche can you get?)
But things turn around when the crew of Serenity arrives (to quote Captain Tightpants here) “just in the nick of time” to rescue Simon and River. They take the town at gunpoint and take Simon and River back. Mal states that Simon and River are part of his crew, whether he likes them or not. The episode ends with everyone having dinner together.
The theme of Safe is family and home. Joss was always fond of “families of choice,” ones that don’t really have blood relations. The flashbacks to Simon and River’s past show the strained relationship that Simon had with his parents. He was right to worry about River, in spite of his parents dismissing that he’s just being silly and missing his sister. His father threatens to cut him off when Simon gets arrested for trying to get information on River’s whereabouts. Of course, we know what he decides.
While Simon and River are in the settler’s clinic, River opens up about how damaged she feels and knows exactly how much her brother sacrificed to save her. She also said “We won’t be here long. Daddy will come and take us home.” Simon thinks that River was referring to their biological father. However, it’s Mal that comes to their rescue. It indicates that in spite of seeing Serenity leave them earlier, River sees Mal as a father figure. Book also says, once he is out of the Alliance infirmary “It’s good to be home.” The fact that the episode ends with everyone sharing a meal together is also a subtle symbol of how the crew of Serenity is slowly becoming a family. In spite of Mal not liking Simon and Jayne wishing they weren’t even there, Simon and River are still part of the family.