Obesity is a risk factor for type 2 diabetes, dyslipidemia, and cardiovascular disease. Dissection of the molecular mechanisms underlying obesity and its relationship to insulin resistance and the metabolic syndrome are essential for developing new strategies for prevention and treatment of these disorders. Both excess adipose tissue and lack of adipose tissue cause insulin resistance and dyslipidemia, suggesting that normal fat is required for the maintenance of systemic glucose and lipid homeostasis. Recent advances in obesity research have led to the recognition that adipose tissue is an active endocrine organ that secretes multiple bioactive factors termed adipokines. Secretion of adipokines provides a link between adipose tissue lipid accumulation and the metabolic function of other tissues such as liver and muscle. Dysregulation of adipokines is emerging as an important mechanism by which adipose tissue contributes to systemic insulin resistance and metabolic disease.