The current study was conducted to describe the prospective relationship between physical activity and academic performance. Prospective studies reporting at least one physical activity or physical fitness measurement and at least one academic performance or cognition measure during childhood or adolescence were identified from searches in PubMed, PsycINFO, Cochrane Central, and Sportdiscus from 1990 through 2010. Titles and abstracts were screened for eligibility and the methodological quality of the studies was rated. Ten observational and four intervention studies were identified. The quality score of the studies ranged from 22% to 75% and two studies were scored as high quality. Methodological quality scores were particularly low for the reliability and validity of the measurement instruments. Based on the results of the best-evidence synthesis, the authors found evidence of a significant longitudinal positive relationship between physical activity and academic performance and concluded that participation in physical activity is positively related to academic performance in children. Because only two high-quality studies were found, future high-quality studies should be conducted to confirm these findings. These studies should thoroughly examine the dose-response relationship between physical activity and academic performance and provide explanatory mechanisms for this relationship. Arch Pediatr Adolesc Med. 2012 Jan;166(1):49-55. PMID: 22213750