Physical inactivity is expanding across all ages in the United States. Research has documented a deficiency in health-related fitness knowledge (HRFK) among elementary- through college-aged students. The need for a credible and reliable resource that provides research-based information regarding the importance of HRFK is significant. The purpose of this article was to examine the relationship between HRFK, physical activity (PA), and physical fitness (PF). This issue is particularly important for physical educators because of the growing concerns over rising obesity and declining levels of PA across the country. HRFK research to this point has indicated three important findings: (1) HRFK is low among elementary-aged students through college-aged students; (2) HRFK has successfully predicted PA and PF levels, though research is limited; and (3) educational interventions such as conceptual physical education (CPE) center on fitness knowledge, and their application has indicated a longitudinal increase in PA and PF levels. This comprehensive review of literature is designed for the use of physical educators considering the adoption of health-related fitness education initiatives with the intent of improving long-term PA and PF.