It is well established that atherosclerosis, the pathological basis of cardiovascular disease (CVD), begins in childhood and progresses steadily between the ages of 15 to 35 years. These adolescent and young adult years are also marked by significant physiological, psychological, and sociodemographic changes that impact both CVD risk factor development and CVD prevention and treatment strategies. In this review, we highlight the importance of the primordial prevention of CVD risk factors before they ever occur and the primary prevention of CVD by treating CVD risk factors in this age group. Although the long time to first CVD event for most young people precludes the availability of clinical trials with hard end-points, findings from epidemiology, health psychology, health services research, and clinical trials with surrogate endpoints are discussed to inform an evidence-based approach to CVD prevention in adolescents and young adults.