Plasma high-density lipoprotein cholesterol (HDL-C) is inversely related to coronary artery disease incidence in both women and men, with a proportionately increasing effect of HDL-C throughout the average (or slightly above average)-to-low concentration range. A substantial body of evidence from major epidemiologic studies has established that this coronary artery disease risk associated with HDL-C is entirely independent of plasma low-density lipoprotein cholesterol, other lipid parameters (triglycerides, total cholesterol), and other nonlipid risk factors. The coronary artery disease relative risk for patients with low levels of HDL-C in conjunction with low total cholesterol is also markedly higher than in patients with a profile of high levels of these 2 lipid parameters. Similarly, the risk associated with a low HDL-C level is of particular significance in patients with established coronary artery disease or with type 2 diabetes, and it is a more pertinent factor to consider when managing dyslipidemia.