An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for atherosclerotic disease. Although the precise mechanism(s) via which LDL promotes atherogenesis remains to be elucidated, the oxidative modification of LDL may be a crucial mechanism. Several lines of evidence support a role for oxidatively modified LDL in atherogenesis. LDL can be oxidatively modified in cell-free systems by transition metals and by all the major cells of the arterial wall. Oxidatively modified LDL (Ox-LDL) is taken up by macrophage scavenger receptors, promoting cholesterol ester accumulation and foam cell formation. It also promotes atherosclerosis by recruitment and retention of monocytes in the intima, by its cytotoxicity toward endothelial cells and by stimulating monocyte adhesion to the endothelium. Several lines of evidence support the in vivo existence of Ox-LDL. The LDL of patients with atherosclerosis are more prone to oxidation; antibodies against epitopes on Ox-LDL have been positively correlated with the progression of atherosclerosis. The oxidation of LDL has been shown to be reduced by antioxidants, and in animal models, these antioxidants decrease atherosclerotic lesion formation. Thus, much evidence supports a role for oxidized LDL in atherogenesis.