PURPOSE OF REVIEW: Probucol is a potent antioxidative drug that has been used for prevention and treatment of atherosclerotic cardiovascular diseases and xanthoma. Probucol has been used as a lipid-lowering drug for a long time especially in Japan, although Western countries quitted its use because of the reduction in serum HDL-cholesterol (HDL-C). This review highlights both basic and clinical studies that provide new insights into the pleiotropic effects of probucol. RECENT FINDINGS: Recently, the mechanisms for the pharmacologic actions of probucol have been elucidated at the molecular level with a special focus on HDL metabolism and its functions. Probucol enhances plasma cholesteryl ester transfer protein activity and hepatic scavenger receptor class B type I, causing a decrease in HDL-C. It also accelerates the antioxidative function of HDL via increase in paraoxonase 1 activity. Recent retrospective analyses of probucol-treated patients with heterozygous familial hypercholesterolemia and those after coronary revascularization demonstrated a strong beneficial effect of probucol on secondary prevention of cardiovascular events and mortality. SUMMARY: Probucol has pleiotropic and beneficial therapeutic effects on cardiovascular system. Although statins are effective for lowering LDL-cholesterol (LDL-C) and reducing coronary heart disease risk, probucol should be considered as an option in case statins are not effective.