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Firefly maintained an ensemble cast that portrayed nine crew members and passengers of the ship, Serenity, dealing with criminals and schemers, Alliance security forces, the utterly psychotic and brutal Reavers, and the mysterious men with "hands of blue"—operatives of a secret agency possibly aligned with The Blue Sun Corporation. The crew is driven by the need to secure enough income to keep their ship operational while keeping a low profile to avoid their adversaries. Their situation is complicated by the differing motivations of the individuals aboard Serenity; the show's brief run hampered further characterization.
All nine of the main characters appeared in every episode, except "Ariel", from which Book is absent.
Nathan Fillion as Malcolm "Mal" Reynolds—the owner and captain of Serenity and former Independent sergeant in the Battle of Serenity Valley. Malcolm grew up on a ranch and was raised by his mother and the ranch hands. In the Unification War, he fought as a platoon sergeant in the 57th Overlanders of the Independent Army, the "Browncoats". He is a cunning, capable leader, and a skilled fighter. Mal's primary motivation is a desire for independence. While he is not above petty theft, smuggling, or even killing to maintain his freedom, he is generally honest in his dealings with others, fiercely loyal to his crew, and adheres to a personal code of honor. He is openly antagonistic toward religion as a result of his experiences during the war.
Gina Torres as Zoe Alleyne Washburne—second-in-command onboard Serenity, a loyal wartime friend of Captain Reynolds, and Wash's wife. Her surname during the Unification War was Alleyne. She was born and raised on a ship and served under Mal during the war as a corporal. Described by her husband as a "warrior woman", she is a capable fighter who keeps calm even in the most dangerous situations. She demonstrates an almost unconditional loyalty to Mal. The only exception noted being her marriage to Wash, which the captain claims was against his orders.
Alan Tudyk as Hoban "Wash" Washburne—Serenity's pilot and Zoe's husband. Deeply in love with his wife, Wash expresses jealousy over his wife's "war buddy" relationship and unconditional support of their captain, most particularly in the episode "War Stories", in which he confronts Mal even as the two of them are being tortured. He joined pilot training just to see the stars, which were invisible from the surface of his polluted homeworld, and he joined Serenity despite being highly sought after by other ships. He is light-hearted and tends to make amusing comments, despite the severity of any situation.
Morena Baccarin as Inara Serra—a Companion, which is the 26th century cross between a geisha, and a courtesan or mistress; she rents and works out of one of Serenity's two small shuttles. As a Companion, Inara enjoys high social standing. Her presence confers a degree of legitimacy and social acceptance that the crew of Serenity would not have without her on board. Inara displays great dignity, civility, and compassion. There is strong romantic tension between her and Mal, who share many character traits, but each frequently objects to the other's work as "whoring" or "petty theft", respectively. Both refuse to act on their feelings and attempt to keep their relationship professional.
Adam Baldwin as Jayne Cobb—a mercenary who first met Mal on the opposite side of a dispute: Mal, while held at gunpoint by Jayne, offered Jayne his own bunk and a higher cut than his current employer, prompting Jayne to switch sides and shoot his then-partners. In the original pilot, "Serenity", he tells Mal that he did not betray him because "The money wasn't good enough." However, he had previously showed reluctance in betraying the captain to an Alliance agent. In "Ariel", he defends betraying Simon and River by claiming he had not intended to betray Mal. He can be depended on in a fight. Occasional hints of intelligence peek through his oafish façade, giving the impression that he acts dumber than he is. Whedon has stated several times that Jayne will ask the questions that no one else wants to. Even though he is a macho character, he has shown a particularly intense fear of Reavers, more so than the rest of the crew. He sends a significant portion of his income to his mother, again suggesting that there is more to his character than what he presents to the rest of the crew.
Jewel Staite as Kaywinnet Lee "Kaylee" Frye—the ship's mechanic. In the episode "Out of Gas", Kaylee reveals she has had no formal training, but keeps Serenity running with an intuitive gift for the workings of mechanical equipment. Jewel Staite describes Kaylee's character as being wholesome, sweet, and "completely genuine in that sweetness", adding "She loves being on that ship. She loves all of those people. And she is the only one who loves all of them incredibly genuinely." She has a crush on Simon Tam. Kaylee is the heart of the ship; according to creator Joss Whedon, if Kaylee believes something, it is true.
Sean Maher as Simon Tam—a trauma surgeon of the first caliber (ranked top 3% in his class at a top core-planet institution), who is on the run after breaking his sister River out of a government research facility. The episode "Safe", reveals that he and River had a privileged upbringing with access to the best education. By rescuing River in spite of his father's severe objections, Simon gave up a highly successful future in medicine. His bumbling attempts at a romantic relationship with Kaylee are a recurring subplot throughout the series. At every turn, he unwittingly foils his own attempts at romance. His life is defined by caring for his sister.
Summer Glau as River Tam—smuggled onto the ship by her brother. She is a brilliant, compassionate, and intuitive child prodigy. Experiments and invasive brain surgery at an Alliance secret facility left her delusional, paranoid, and at times violent—though her uncanny ability to seemingly sense things before they happen leaves questions as to where the delusions end and reality begins. The experiments seem to have made her a psychic. The experiments also gave her an innate knack for hand-to-hand combat, and she is capable of killing or incapacitating several opponents in a fight with ease. She gets frequent fits of anxiety and experiences post-traumatic flashbacks of her time in the Alliance facility. Her mental instability and uncanny abilities, paired with several erratic and violent acts, are a recurring source of fear and doubt among the crew, especially with Jayne, whom she once slashed with a knife. Jayne frequently requests that River and Simon be taken off the ship.
Ron Glass as Derrial Book—a Shepherd (equivalent to a pastor). Although presented as a devout Christian, Book has profound, unexplained knowledge about criminal activities, police corruption, and military strategy, tactics, and weapons. In "Safe", he was shown to have sufficient status in the Alliance to receive emergency medical treatment from an Alliance ship. He is also proficient in hand-to-hand combat and the use of firearms. He maintains his objection to violence even during a rescue mission, joining the fight while stating that although the Bible specifically disallows killing, it is "somewhat fuzzier on the subject of kneecaps." Book is a moral guide for Mal and the rest of the crew, a voice of reason, conscience, and spirituality. He also gets along well with the amoral mercenary Jayne, with the two spotting each other while working out using a bench press. His hidden backstory would have been gradually revealed had the series continued but was instead explored in the 2010 comic book The Shepherd's Tale.