Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of coronary artery disease events. Data in animals indicate that increasing HDL cholesterol levels decreases progression of atherosclerosis. Some clinical trials suggest a benefit from increasing HDL cholesterol levels, but additional data in humans are needed. Nevertheless, in patients with, or at high risk for, coronary artery disease, a decision to institute drug therapy that includes an effort to increase HDL cholesterol levels is reasonable based on available data. Several clinical trials are underway to determine the most effective drug therapy for decreasing the risk of coronary artery disease associated with low HDL cholesterol levels.