Human space flights in microgravity conditions lead to a spectrum of changes in the physiological and biomechanical properties of the central nervous system. These changes can pose challenges to the diagnosis, management, and recovery process for astronauts who sustain any neurotrauma. Understanding these interactions can be of particular importance to ensure the safety of astronauts and the development of space medicine, where valuable insight can be provided into neurotrauma care based on the experiences gained on Earth. The present narrative review discusses the neurophysiological effects of microgravity, its implications for neurotrauma, diagnostic challenges, and potential therapeutic interventions.