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An increased amount of adipose tissue or its disproportionate distribution between central and peripheral body regions is related to the development of insulin resistance, type 2 diabetes mellitus, dyslipidemia, atherosclerosis, and coronary artery disease. Until recently, adipose tissue was regarded as a storage depot for lipids. It is now viewed as a hormonally active organ that plays a crucial metabolic role. The most important products of adipose tissue collectively referred to as adipocytokines, include adiponectin, leptin, tumor necrosis factor–alpha (TNF-α), interleukin-6 (IL-6), resistin, plasminogen-activating inhibitor–I (PAI-1), and angiotensinogen. These low and medium molecular weight proteins play an important role in the adipose tissue physiology and are believed to be a link between obesity, insulin resistance and endothelial dysfunction. This review describes the metabolic role of two of these proteins, adiponectin and leptin, in relation to insulin sensitivity.