In recent years, we have learned that adipocytes are not merely inert storage depots for triglycerides but rather highly active cells with potent autocrine, paracrine and endocrine functions. Adipose tissue secretes a large number of physiologically active polypeptides. Although leptin remains one of the best-studied examples of an adipocyte-specific secretory factor, recent reports describe potent physiological activities for another adipocyte-specific secreted protein, adipocyte complement-related protein of 30 kDa (Acrp30). Full-length versions of Acrp30 or its proteolytic fragments decrease the postprandial rise of plasma free fatty acids and improve postabsorptive insulin-mediated suppression of hepatic glucose output. A strong correlation between plasma Acrp30 levels and systemic insulin sensitivity is well established and the protein has putative anti-atherogenic properties that are relevant for the prevention of formation of atherosclerotic plaques. The current challenge is to understand the molecular mechanisms through which the protein exerts its multiple functions.