Hypercholesterolemia is associated with increased risk of premature cardiovascular disease in adults, while early atherosclerotic lesions (reversible fatty streaks and non reversible fibrous plaques) are also associated with cardiovascular risk factors including low density lipoprotein-cholesterol (LDL-C). Although LDL-C is a risk factor that should be addressed in high risk children such as those with familial hypercholesterolemia, it is unclear, at present, whether there is a certain plasma LDL-C level that would call for an intervention regardless of the etiology of elevated LDL-C. Therefore, at present, screening the entire population to identify subjects with hypercholesterolemia is not justified. The aims of this review are to familiarize the reader with inherited diseases that are associated with elevated LDL-C and discuss the management of children with elevated LDL-C.