The weightless environment of space imposes specific physiologic adaptations on healthy astronauts. On return to Earth, these adaptations manifest as physical impairments that necessitate a period of rehabilitation. Physiologic changes result from unloading in microgravity and highly correlate with those seen in relatively immobile terrestrial patient populations such as spinal cord, geriatric, or deconditioned bed-rest patients. Major postflight impairments requiring rehabilitation intervention include orthostatic intolerance, bone demineralization, muscular atrophy, and neurovestibular symptoms. Space agencies are preparing for extended-duration missions, including colonization of the moon and interplanetary exploration of Mars. These longer-duration flights will result in more severe and more prolonged disability, potentially beyond the point of safe return to Earth. This paper will review and discuss existing space rehabilitation plans for major postflight impairments. Evidence-based rehabilitation interventions are imperative not only to facilitate return to Earth but also to extend the safe duration of exposure to a physiologically hostile microgravity environment.