Low high-density lipoprotein (HDL) cholesterol is associated with increased risk of coronary heart disease (CHD). Ongoing investigation into the mechanisms whereby HDL cholesterol might provide protection from atherosclerosis and clinical disease has resulted in improved understanding of the role of HDL in removal of cholesterol from the arterial wall and has suggested a number of strategies for augmenting the beneficial activities of the lipoprotein. Current drug options for increasing HDL cholesterol levels include the statins, fibrates, and niacin. Strategies in development for increasing the function of HDL or apolipoprotein A-I and thereby reducing atherosclerotic progression include use of agents to upregulate the adenosine triphosphate-binding cassette transporter in vessel wall macrophages to increase cholesterol efflux from these cells; use of agents to stimulate endogenous apoA-I synthesis; administration of apoA-I, apoA-I Milano, apoA-I-mimetic peptides, or delipidated HDL; and use of cholesteryl ester transfer protein inhibitors.