Radiation environment in long-term exploration missions is scrutinized in the context of the risks of deterministic and stochastic effects of radiation. The probability of severe radiation damage as a result of solar flares is very low; nevertheless, interplanetary crews must be provided with the appropriate protective agents, including pharmacological ones. The current nomenclature of radioprotectors comprises short-term agents against acute radiation damage. Among them, B-190 preparation has been distinguished by particularly high effectiveness, large window of radioprotection, and good tolerance even during the exposure to extreme factors of space flight. The therapeutic regimens for B-190, separately and in combination with radioprotectors from aminothiol family, have been developed for the treatment duing multiple solar events. The efficiency of radioprotectors can be substantially enhanced by the local shielding of abdomen and pelvis. The most promising nonspecific stimulators of total resistance of the body are riboxin (inosine) and the combined preparation aminotetravit, as well as the tocopherol and retinol (vitamins E and A). The possibility of B-190 combination therapy with riboxin and aminotetravit has been considered. The cytokine neupogen (G-CSF) is also considered as a candidate agent for early therapy of acute radiation syndrome. Attention has been paid to the possible development of chronic oxidative stress in long-term exploration missions. The significance of adequate nutrition supplemented with fresh vegetables as a source of the most valuable bioflavonoids has been highlighted. The antioxidants L-selenomethionine and melatonin proved to be efficient against heavy nuclei of galactic radiation. The possible scenarios of implementation of the effects of natural antioxidants under oxidative stress low-rate-dose galactic radiation have been considered.