Low-density lipoprotein (LDL) apheresis offers an additional approach to lipid lowering in patients with severe hypercholesterolemia who fail to respond adequately to diet and drug therapy. Well-defined criteria for patient selection have yet to be established for LDL apheresis. This study proposes guidelines based on whether coronary artery disease (CAD) is present and on the degree of LDL cholesterol elevation after treatment with diet and maximal drug therapy. It is reasonable to consider LDL apheresis therapy for: (1) patients with CAD and LDL cholesterol levels > 190 mg/dl; (2) patients without CAD, but at high risk for disease due to an LDL cholesterol level > 250 mg/dl, a first-degree relative with premature CAD, and the presence of > or = 1 additional risk factor. In addition, LDL apheresis is recommended for the management of all patients with homozygous familial hypercholesterolemia due to the very high risk of CAD and the poor response to usual lipid-lowering treatments.