Observational studies provide overwhelming evidence that a low high-density lipoprotein (HDL)-cholesterol level increases the risk of coronary events, both in healthy subjects and in patients with coronary heart disease. Based on in vitro experiments, several mechanistic explanations for the atheroprotective function of HDL have been suggested. However, few of these were verified in vivo in humans or in experiments with transgenic animals. The HDL functions currently most widely held to account for the antiatherogenic effect include participation in reverse cholesterol transport, protection against endothelial dysfunction, and inhibition of oxidative stress. This review summarizes current views on the molecular mechanism underlying these atheroprotective effects of HDL.