Reduction of plasma low-density lipoprotein (LDL) cholesterol reduces cardiovascular events and total mortality; however, many patients with premature coronary artery disease do not have elevated LDL cholesterol levels but instead have elevated triglycerides or low high-density lipoprotein (HDL) cholesterol level (or both), and data suggest that intervention to modulate these lipoprotein fractions may reduce cardiovascular risk. Lipoprotein(a) (Lp(a)) is another lipoprotein that has been recognized as an heritable independent risk factor for premature cardiovascular disease. Patients with thyroid disorders, nephrotic syndrome, and end-stage renal disease and patients who have had solid organ transplantation present unique challenges in the management of hyperlipidemia. This article reviews these topics.