Definition: Microgravity introduces diverse pathological and various physiological changes to the human body, including intraocular pressure. Astronauts may develop a constellation of symptoms and signs including optic disc edema, choroidal folds, and a hyperopic shift from the flattening of the globe. These ocular findings have been collectively termed spaceflight-associated neuro-ocular syndrome (SANS). SANS is a condition that is unique to long-duration spaceflight. The precise pathogenesis of SANS remains ill-defined, but several hypotheses have been proposed that may be influenced by intraocular pressure. Countermeasures for SANS research also include techniques that impact intraocular pressure. In this article, we discuss intraocular pressure during spaceflight, the translaminar pressure gradient, SANS and potential SANS countermeasures, and the potential for glaucomatous damage during spaceflight.