Objective: To describe the contribution of adipocytes and adipose tissue to increased cardiometabolic risk as well as the mechanisms by which adipose tissue and obesity contribute to dysglycemia, dyslipidemia, hypertension, and a prothrombotic, inflammatory state favoring atherogenesis. Methods: A review was undertaken of the relevant available reports, compiled by means of a search (PubMed) of the English-language literature published between 1994 and 2010. Results: Coronary risk factors cause susceptibility to development of atherosclerosis. Traditional coronary risk factors are obesity, smoking, hypertension, diabetes, elevated serum cholesterol levels, male sex, advancing age, and a family history of early coronary events. The currently preferred term of cardiometabolic risk encompasses both the traditional coronary risk factors and the additional contributing factors of insulin resistance, atherogenic dyslipidemia, physical inactivity, unhealthful eating, inflammation, and hypercoagulation. The accumulation of adipose tissue (adiposity) and dysfunctional adipose tissue (adiposopathy) contribute to most, if not all, of the cardiometabolic risk factors. Adipose tissue promotes atherosclerosis through several different pathologic mechanisms, which are reviewed in this report. The treatment of obesity should focus on reducing fat mass and minimizing adipocyte dysfunction. Conclusion: Adipose tissue contributes to the development of insulin resistance, hyperglycemia, atherogenic dyslipidemia, and arterial hypertension and favors a prothrombotic and proinflammatory state. Adipose tissue dysfunction increases cardiometabolic risk through a variety of mechanisms. (Endocr Pract. 2010;16:692-698)