Purpose <p>A main concern of space agencies planning manned missions to the Moon or Mars is visual impairment in the microgravitational environment. In a previous review dating back to 2019 we provided an overview of this topic. In that paper, we recalled that, aside from radiation, the most threatening menace for vision in space is a prolonged condition of microgravity, responsible for the so-called Spaceflight-Associated Neuro-ocular Syndrome (SANS), This review intends to update the previous one, providing insights on its etiopathogenesis.</p> Methods <p>Bibliographic research was carried out on PubMed, Google Scholar, and other resources supporting biomedical literature, starting with the following keywords: SANS, Spaceflight-Associated Neuro-ocular syndrome, Astronauts/Space + Eye/Vision. The references in each selected paper were analyzed. Overall, 218 studies were examined, 122 of them were considered suitable for our purposes.</p> Results <p>SANS is a multifactorial syndrome caused by the cephalad fluid shift that occurs in microgravity. This hemodynamic perturbation is assumed to lead to compartmentalization of the cerebrospinal fluid in the subarachnoid perioptic space associated with reduced glymphatic clearance, mildly elevated intracranial pressure in some cases, and other pathophysiological phenomena. Risk factors have been identified and further investigations are ongoing.</p> Conclusion <p>A comprehensive understanding of the etiopathology of SANS and identification of predisposing factors among astronauts is essential to mitigate or even better neutralize its deleterious effects on the visual system, in the perspective of long-duration space missions on the Moon and the Red Planet.</p>