It is likely that the 21st century will be characterized by human space exploration and colonization. The International Space Station (ISS) already provides a living environment for humans outside the Earth; a manned mission to Mars is planned for 2025; exploration of other planets (e.g. Jupiter) are also planned; space tourism may soon become a reality. A major area of concern is the possible detrimental effects on health (including cancer, cataracts, hereditary effects and neurological disorders) caused by the exposure to galactic cosmic rays (GCR) and solar particle events (SPE). Uncertainties in space radiation risk for interplanetary missions are substantially high (400–1500% according to NASA estimates), and international scientific cooperation is needed to reduce these uncertainties before manned exploration missions start. Even if uncertainties in risk assessment will be reduced in the next few years, there is little doubt that appropriate countermeasures have to be taken to reduce the exposure or the biological damage produced by cosmic radiation. In addition, it is necessary to develop appropriate countermeasures against SPE, which can produce acute effects, even life threatening, for inadequately protected crews. Strategies that may prove to be effective in reducing exposure, or the effects of the irradiation, include shielding, administration of drugs or dietary supplements to reduce the radiation effects, crew selection based on a screening of individual radiation sensitivity. It is foreseeable that research in passive and active radiation shielding, radioprotective chemicals, and individual susceptibility will boost in the next years to provide efficient countermeasures to the space radiation threat.