The oxidation of LDL is thought to be a major contributor to the development of atherosclerosis. Considerable descriptive evidence has been accumulated showing that oxidized LDL promotes pro-atherogenic events. However, direct evidence that oxidized LDL causes atherosclerosis is lacking. This article summarizes the results of recent studies that demonstrate how oxidized LDL affects cellular function, and highlights key issues that should be addressed to link LDL oxidation with atherosclerosis.