There appear to be compelling evidences presenting adiponectin as a key regulator of energy homeostasis. Over the past 10 years, much work has been done to identify the molecular mechanisms by which adiponectin functions in the body. We and other groups have demonstrated that adiponectin activates multiple signaling pathways, which mediate its anti-diabetic, anti-atherogenic and anti-inflammatory functions. Comprehensive analysis of the mechanism of adiponectin action may allow us to elucidate the etiology of metabolic syndrome associated diseases including diabetes and cardiovascular diseases, where dysfunction of adiponectin may contribute to pathogenesis of diseases. While regulation of adiponectin gene expression or secretion remains an interesting topic in studies of cell metabolism, further intensive studies are necessary to illustrate the molecular mechanisms. Importantly, identification of molecules in the adiponectin signaling pathways and in the regulation of adiponectin gene expression may provide novel targets for therapeutic drugs.