Objective: There is suggestive evidence that exercise may have a greater effect on visuo-spatial memory, compared to other memory types. However, we have a limited understanding as to the mechanisms through which exercise may subserve visuo-spatial memory. Thus, the purpose of this review is to evaluate the extent to which exercise may influence visuo-spatial memory, whether exercise can attenuate drug- and diseased-induced declines in memory, and determine the underlying mechanisms of these relationships. Methods: We employed a systematic review approach. We identified studies using electronic databases, including PubMed, PsychInfo, Sports Discus and Google Scholar. Results: In total, we identified 32 articles. Among these, 2 were among humans and 30 were conducted in animal models. There was strong evidence sup- porting the facilitative role of chronic exercise in visuo-spatial memory improvements, as well as attenuation of drug- and diseased-induced memory decline. There are various mechanisms through which chronic exercise may influence visuo-spatial memory, including increased neuro-genesis, angiogenesis, improved neural efficiency, CB1 receptor signaling, activation of H₂ receptors, and increased number of synaptic structures (eg, AMPA and NMDA receptors). Conclusion: Exercise may help to enhance visuo-spatial memory.