Human space flight poses several challenges to human health, such as microgravity, space radiation, and prolonged confinement. Humans are anatomically and physiologically adapted to the gravitation on earth, and microgravity affects crucial functions. We review the pathophysiological consequences of spaceflight on the sensomotoric, cardiovascular, cerebral, and musculoskeletal systems, as well as effects of space radiation and psychosocial considerations. We also look at the medical capabilities in space, and different research methods on earth and in space.