Siglo XXVI. Tras ganar la guerra Civil Galáctica, las dos grandes potencias mundiales, EE.UU. y China, se unen para formar un gobierno totalitario llamado Alianza Universal. El Capitán Malcolm Reynolds es un curtido veterano de la guerra que se gana la vida alquilando su nave, la Serenity y buscando trabajos al margen de la ley. Su única familia es una pequeña y leal tripulación de disidentes y rebeldes. Cuando Malcom embarca a dos nuevos pasajeros, un médico y su inestable hermana, que está dotada de poderes telepáticos, enseguida descubre que ambos son fugitivos de la Alianza y que ésta no se detendrá hasta dar con la chica. Y, en efecto, la tripulación de la Serenity se verá atrapada entre el poderoso ejército de la Alianza y los Ravers, salvajes bárbaros que vagan por los confines del espacio. Así las cosas, empiezan a darse cuenta de que quizá el mayor peligro se encuentra a bordo de la Serenity.
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