Currently, there is considerable interest in the physical activity and cardiovascular disease (CVD) risk factors of youth in North America and other developed countries. The central question to this paper is, what is the role of physical activity in the primary prevention of CVD? Three subquestions are explored: what are the current levels and prevalence of physical activity and CVD risk factors in North American youth?; what is the association between physical activity and CVD risk factors in children and adolescents?; and what is the influence of childhood physical activity on subsequent adult cardiovascular health? The number of youth meeting physical activity recommendations varies by measurement procedures, age and sex. In general, physical activity levels decline during adolescence. Aerobic fitness remains stable in boys and gradually declines during adolescence in girls. The prevalence of overweight and the emergence of type 2 diabetes in children and adolescents have increased over the past few decades. Although the association is weak and causal inference cannot be drawn, physical activity explains a small amount of the variance in CVD risk factors during childhood and adolescence, particularly at the extremes. Childhood overweight increases the risk of adult overweight, the clustering of other CVD risk factors, coronary artery calcification in adulthood, and all-cause and CVD mortality. Future studies should consider the measurement of physical activity, physical activity-genotype interactions, biobehavioral approaches to the prevention and treatment of obesity and comorbidities, and emerging risk factors. Prospective cohort studies are also warranted to further examine the influence of childhood physical activity on subsequent health outcomes.