Spaceflight (SF) increases the risk of developmental, regenerative, and physiological disorders in animals and humans. Astronauts, besides bone loss, muscle atrophy, and cardiovascular and immune system alterations, undergo ocular disorders affecting posterior eye tissues, including the retina. Few studies revealed abnormalities in the development and changes in the regeneration of eye tissues in lower vertebrates after SF and simulated microgravity. Under microgravity conditions, mammals show disturbances in the retinal vascular system and increased risk of oxidative stress that can lead to cell death in the retina. Animal studies provided evidence of gene expression changes associated with cellular stress, inflammation, and aberrant signaling pathways. Experiments using retinal cells in microgravity-modeling systems in vitro additionally indicated micro-g-induced changes at the molecular level. Here, we provide an overview of the literature and the authors’ own data to assess the predictive value of structural and functional alterations for developing countermeasures and mitigating the SF effects on the human retina. Further emphasis is given to the importance of animal studies on the retina and other eye tissues in vivo and retinal cells in vitro aboard spacecraft for understanding alterations in the vertebrate visual system in response to stress caused by gravity variations.