The purposes of this article were to (1): review recent studies of relations between physical activity and cardiometabolic biomarkers of youths (2); highlight areas in which additional research is needed; and (3) make recommendations for preventive interventions. Observational studies show that youths who engage in high amounts of moderate-vigorous physical activity display a more favorable cardiometabolic biomarker profile than youths who engage in lesser amounts of moderate-vigorous physical activity. Intervention studies in obese youths show that favorable changes in biomarkers are produced by moderate-vigorous physical activity doses of 150–180 min/week. However, for nonobese youths, intervention studies suggest that such doses are not effective; higher moderate-vigorous physical activity doses of approximately 300 min/week seem necessary. Continuing a physically active lifestyle from childhood into the adult years will enable people to maintain less end-organ damage and lower rates of morbidity and mortality from cardiovascular disease and type 2 diabetes.