Although a consensus developed early in the space program that complex operations could be performed successfully in space, it appears that humans are slower there than on Earth. Recent experiments aimed at determining the cause of this slowing suggest that central cognitive operations are unaffected but that perceptual-motor performance is degraded under certain circumstances. Two hypotheses have been proposed to account for this degradation-the direct effects of microgravity on the central nervous system and the non-specific effects of multiple stressors. Present evidence can be interpreted as supporting either hypothesis and further experiments are required to settle the question. This issue has practical implications since the countermeasures needed to ameliorate or prevent performance deficits will differ according to which hypothesis is correct. Understanding and ameliorating performance deficits will help ensure safe operations aboard the International Space Station and during a mission to Mars.