The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, effectively reduce coronary morbidity and mortality in high-risk adults. They are also some of the most widely prescribed medications in the United States. Their use in pediatrics, however, remains circumscribed. In this article we review the cholesterol hypothesis and focus on the knowledge base of the use of statins in adults and children. We pay particular attention to the known effects of statins in primary and secondary prevention of cardiovascular events. The toxicities of statins and their limitations in pediatrics are then considered. The use of statins in conjunction with noninvasive modalities of assessing atherosclerotic burden are also reviewed. Finally, we suggest methods to advance the use of statins in childhood that introduce their potential benefits to those individuals at highest risk for future events.