Treatment of hypercholesterolemia in youth is predicated on the knowledge that we can identify those youth with this atherosclerotic risk factor most likely to develop premature cardiovascular disease. Unfortunately, this is not the case. Before we can adequately address appropriate lipid-lowering therapies in this special population, we must address and resolve current barriers related to screening and diagnosis. In this article, we describe some of the opportunities and obstacles that clinicians and policy makers confront when applying the current pediatric guidelines focused on screening and treating hypercholesterolemia in the pediatric population.