It is well known that performance decrements occur in astronauts during and after gravity level transitions. Illusions are commonly felt in orbit as well disorientation and perceptual limitations, mainly due to both psycho-physiological changes and adaptation and lack of familiar points of reference in the space environment. Studies performed during previous space missions showed several changes occurring in different gravity conditions, pointing out, for example, that colors and shadows were misleading, the depth and distance perception were weakened, and the linear perspective was lost. Visual perception is of primary importance for spatial orientation and object recognition because the static vestibular (otolithic) and proprioceptive signals are absent when free-floating. Consequently, astronauts become increasingly dependent on vision to perceive motion and orientation. All these factors play an important role in the adaptation of humans to spaceflight that needs to be analyzed to understand the underlying mechanisms that regulate human psycho-physiological adaptive process to changing gravity. Human psycho-physiological health has to be safeguarded and possibly improved when long-term human space missions are programmed in the near future.