Future manned missions in deep space toward Moon and Mars represent one of the greatest challenges for radiological protection, which task is to mitigate risks for human life raised by the hostile space radiation environment. The prolonged exposure of astronauts to cosmic rays, mainly ion fields of galactic or solar origin, with a large dynamical behavior in time and space with a wide range of kinetic energies, may result in an unacceptable life risk for the next deep space manned missions. Indeed, these ions can deliver significant doses to astronauts by directly hitting human tissues as well as exposing them to secondary particles (neutron and high-LET nuclear fragments) produced by their interaction with space habitat materials. This radiation environment is very different from work environments on Earth, for example, in nuclear power plants or nuclear medicine departments, for which radioprotection was historically developed. Workers on Earth are mainly exposed to photons ($$\textrm{X}$$
X
-rays and $$\gamma$$
γ
-rays), to $$\alpha$$
α
- and $$\beta$$
β
-particles and neutrons, with lower energies than those in space. This difference marks a significant change in the methodological approach of the radioprotection in space compared to that on ground. The review presents the basic principles of radiation protection in space compared to that on ground and the strategies that must be implemented to mitigate risks in manned missions. In particular, the principles of the integrated multidisciplinary approach proposed by NASA and other space agencies for human space exploration are also discussed, with emphasis on the synergies among the various countermeasures proposed.