Space exploration is a dream of mankind. However, this intriguing environment is not without risks. Life, and the human body, has developed all over evolution in the constant presence of gravity, especially from the moment on when living creatures left the ocean. When this gravitational force is no longer acting on the body, drastic changes occur. Some of these changes occur immediately, others progress only slowly. In the past 40 years of human space flight (first orbital flight by Yuri Gagarin on 12 April, 1961) several hazards for the human body have been identified. Bone mineral density is lost, muscle atrophy and cardiovascular deconditioning occur; pulmonary function, fluid regulating systems of the body, the sensory and the balance system are all disturbed by the lack of gravity. These changes in human physiology have to be reversed again when astronauts return to earth. This can cause adaptation problems, especially after long-duration space flights. Also the reaction of human physiology to radiation in space poses a huge risk at this moment. In this review the accent will be on cardiovascular function in space: how normal function is modified to reach a new equilibrium in space after short- and long-duration exposure to microgravity. In order to make long-duration space flight possible the mechanisms of this physiological adaptation must be understood to full extent. Only with this knowledge, effective countermeasures can be developed.