There is a substantial body of literature related to the effects of a single session of exercise on cognitive performance. The premise underlying this research is that physiological changes in response to exercise have implications for cognitive function. This literature has been reviewed both narratively and meta-analytically and, although the research findings are mixed, researchers have generally concluded that there is a small positive effect. The purpose of this meta-analysis was to provide an updated comprehensive analysis of the extant literature on acute exercise and cognitive performance and to explore the effects of moderators that have implications for mechanisms of the effects. Searches of electronic databases and examinations of reference lists from relevant studies resulted in 79 studies meeting inclusion criteria. Consistent with past findings, analyses indicated that the overall effect was positive and small (g = 0.097 n = 1034). Positive and small effects were also found in all three acute exercise paradigms: during exercise (g = 0.101; 95% confidence interval [CI]; 0.041–0.160), immediately following exercise (g = 0.108; 95% CI; 0.069–0.147), and after a delay (g = 0.103; 95% CI; 0.035–0.170). Examination of potential moderators indicated that exercise duration, exercise intensity, type of cognitive performance assessed, and participant fitness were significant moderators. In conclusion, the effects of acute exercise on cognitive performance are generally small; however, larger effects are possible for particular cognitive outcomes and when specific exercise parameters are used.