Astronauts during space flight and microgravity face a range of physiological and pathological challenges that include variations in intraocular pressure (IOP). Prior research has documented an initial elevation in IOP during space travel and thus it is a theoretic risk factor for the development of or progression of glaucoma [1]. Glaucoma is a very common terrestrial ocular disease defined by a degeneration of retinal ganglion cells, structural optic nerve damage, and subsequent functional reduction in the visual field [2]. In addition, astronauts after long-duration spaceflight may develop optic disc edema, choroidal folds, and a hyperopic shift from the flattening of the globe. These findings have collectively been termed SANS. The precise etiology of SANS is not completely understood; however, several proposed hypotheses include orbital and cephalad fluid shifts during microgravity. These potential mechanisms have implications for the possible role of IOP in the pathogenesis of SANS. The objective of this article is to investigate the relationship among alterations in IOP during space travel, the significance of the trans-laminar pressure gradient, the risk for development of or progression of glaucoma, and potential countermeasures.