Cardiovascular disease accounts for an overwhelming proportion of the morbidity and mortality suffered by patients with obesity and type 2 diabetes mellitus, and recent work has elucidated several potential mechanisms by which increased adiposity enhances cardiovascular risk. Excess adipose tissue, especially in certain compartments, leads to reduced insulin sensitivity in metabolically responsive tissues, which is frequently associated with a set of cardiovascular risk factors, including hyperinsulinemia, hypertension, dyslipidemia, and glucose intolerance. Increasing attention has also been paid to the direct vascular effects of plasma proteins that originate from adipose tissue, especially adiponectin, which exhibits potent antiinflammatory and antiatherosclerotic effects. This brief review will summarize recent work on the vascular actions of adiponectin, which complements the growing body of information on its insulin-sensitizing effects in glucose and lipid metabolism. Adiponectin is now a recognized component of a novel signaling network among adipocytes, insulin-sensitive tissues, and vascular function that has important consequences for cardiovascular risk.