Obesity is a recognized risk factor for cardiovascular disease. Because the prevalence of obesity is rising in industrialized as well as developing nations, it is important to understand the mechanisms by which obesity targets the vascular system. A metabolic syndrome of insulin resistance is provoked by obesity, and this results in the dysregulation of a number of adipocyte-derived factors, which favors atherosclerosis. This review focuses on how products of the adipocyte, including free fatty acids and "adipo"-cytokines, may mediate the effect of obesity on insulin resistance and atherosclerosis.