Recent research has shown that adi-pose tissue is not simply an inert storage depot for lipids but is also an important endocrine organ that plays a key role in the integration of endocrine, metabolic, and inflammatory signals for the control of energy homeostasis. The adipocyte has been shown to secrete a variety of bioactive proteins into the circulation. These secretory proteins, which have been collectively named adipocytokines (1), include leptin (2), tumor necrosis factor (TNF)-α (3), plasminogenactivator inhibitor type 1 (PAI-1)(4), adipsin (5), resistin (6), and adiponectin (7). Adiponectin, the gene product of the adipose most abundant gene transcript 1 (apM1)(7), is a novel and important member of the adipocytokine family. Adiponectin cDNA was first isolated by largescale random sequencing of the human adipose tissue cDNA library (7). It is a collagen-like protein that is exclusively synthesized in white adipose tissue, is induced during adipocyte differentiation, and circulates at relatively high (microgram/milliliter) concentrations in the serum. Both murine and human forms of adiponectin have been isolated independently by several groups, and various descriptive names have been given to the same compound by different investigators: adipocyte complement-related protein of 30 kilodalton (Acrp30)(8), Adipo Q (9), and gelatin binding protein of 28 kilodalton (GBP28)(10). The former two are murine analogs and the latter the human counterpart. Throughout this review, we will be referring to the protein by its most commonly used name, adiponectin. Adiponectin has been postulated to play an important role in the modulation of glucose and lipid metabolism in insulin-sensitive tissues in both humans and animals. Decreased circulating adiponectin levels have been demonstrated in genetic and diet-induced murine models of obesity (11), as well as in dietinduced forms of human obesity (12). Low adiponectin levels have also been strongly implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy (11). In humans, plasma levels of adiponectin are significantly lower in insulin-resistant states including type 2 diabetes (13) and can be increased upon administration of the insulin-sensitizing thiazolidinedione (TZD) class of compounds (14–17). Plasma adiponectin levels in diabetic subjects with coronary artery disease (CAD) are lower than in diabetic patients without CAD, suggesting that adiponectin may have anti-atherogenic properties (18). In studies done on human aortic endothelial cells, adiponectin has been shown to dose-dependently decrease the surface expression of vascular adhesion molecules known to modulate endothelial inflammatory responses (19). It also inhibits proliferation of vascular smooth muscle cells (20) and concentrates within the vascular intima of catheter-injured vessels (21). In clinical studies, low adiponectin levels have been associated with an atherogenic lipid profile (18, 22). The association of low adiponectin levels with obesity, insulin resistance, CAD, and dyslipidemia indicates that this novel protein may be an important new marker of the metabolic syndrome. This article will review the current understanding about the structure, function, and metabolic effects of adiponectin and provide insight into its potential clinical relevance.