Pharmacological agents used to treat primary and combined hyperlipidemia reduce cardiovascular disease morbidity and mortality. Risk reduction has been attributed to improvements in blood lipid and lipoprotein characteristics. However, each class of available lipid-lowering drugs has been shown to exhibit pleiotropic effects that broaden their anticipated actions. Indeed, the results of a growing number of available studies suggest that a strong relationship exists between pharmacological reductions in blood lipids and circulating concentrations of the adipose tissue derived protein, adiponectin. Adiponectin is the most abundantly secreted protein from adipose tissue and has been shown to decrease hepatic glucose production, increase fatty acid oxidation in liver and skeletal muscle, and decrease vascular inflammation. In this chapter, we present a comprehensive analysis of the effects of the available classes of lipid-lowering drugs (statins, fibrates, niacin, and omega-3-fatty acids) on circulating adiponectin and the known mechanisms which produce these important events. © 2012 Elsevier Inc.