<p>Solar system exploration is a grand endeavour of humankind. Space agencies have been planning crewed missions to the Moon and Mars for several decades. However, several environmental stress factors in space, such as microgravity and cosmic radiation, confer health risks for human explorers. This Review examines the effects of microgravity and exposure to cosmic radiation on the CNS. Microgravity presents challenges for the brain, necessitating the development of adaptive movement and orientation strategies to cope with alterations in sensory information. Exposure to microgravity also affects cognitive function to a certain extent. Recent MRI results show that microgravity affects brain structure and function. Post-flight recovery from these changes is gradual, with some lasting up to a year. Regarding cosmic radiation, animal experiments suggest that the brain could be much more sensitive to this stressor than may be expected from experiences on Earth. This may be due to the presence of energetic heavy ions in space that have an impact on cognitive function, even at low doses. However, all data about space radiation risk stem from rodent experiments, and extrapolation of these data to humans carries a high degree of uncertainty. Here, after presenting an overview of current knowledge in the above areas, we provide a concise description of possible counter-measures to protect the brain against microgravity and cosmic radiation during future space missions.</p>