Data support the relevance of blood cholesterol levels, particularly high levels of low-density lipoprotein (LDL), in the pathogenesis and progression of atherosclerosis. A strong and continuous relationship between dyslipidemia and vascular morbidity and mortality has been established. The initial approach to treating dyslipidemia consists of lifestyle modifications followed by pharmacologic therapy, usually beginning with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Some patients with familial hypercholesterolemia (FH) fail to achieve their LDL goal despite aggressive pharmacologic therapy. In certain cases, LDL apheresis may be an effective therapeutic option. In the United States, LDL apheresis is approved for homozygous FH patients with an LDL cholesterol level >/= 500 mg/dL. For patients with heterozygous FH, LDL apheresis may be offered if their LDL is >/= 300 mg/dL, or >/= 200 mg/dL with known coronary artery disease, despite maximum medical treatment. This review focuses on the principles and methods of LDL apheresis, its potential benefit in clinical care, and its current indications.