Although statin therapy has revolutionized management of coronary heart disease (CHD), the lowering of low-density lipoprotein cholesterol (LDL-C) levels is not the whole story. Increased plasma concentrations of high-density lipoprotein cholesterol (HDL-C) have a cardioprotective effect that is just as important for reducing risk of heart attack and stroke. In this article, Dr McGovern examines the evidence that provides the rationale for HDL-C as a therapeutic target for cardiovascular risk reduction.