Reverse cholesterol transport identifies a series of metabolic events resulting in the transport of excess cholesterol from peripheral tissues to the liver. High-density lipoproteins (HDL) are the vehicle of cholesterol in this reverse transport, a function believed to explain the inverse correlation between plasma HDL levels and atherosclerosis. An attempt to stimulate, by the use of drugs, this transport process may hold promise in the prevention and treatment of arterial disease. Among the agents affecting lipoprotein metabolism, only probucol exerts significant effects on reverse cholesterol transport, by stimulating the activity of the cholesteryl ester transfer protein and, consequently, altering HDL subfraction composition/distribution. Another approach to the stimulation of reverse cholesterol transport consists of raising plasma HDL levels; studies in animals, either by exogenous supplementation or by endogenous overexpression, have shown a consistent benefit in terms of atherosclerosis regression and/or non-progression. Thus, it is time to consider different future treatments of atherosclerosis, combining the classical lipid-lowering treatments with innovative methods to promote cholesterol removal from the arterial wall.