Excess visceral fat can regulate insulin sensitivity and energy metabolism by releasing adipokines into the circulation which then bind with their cognate receptors in various tissues and alter glucose and lipid metabolism. Circulating levels of adiponectin, which promotes glucose uptake into skeletal muscle and increases fat oxidation rates, are decreased in obesity. Strategies to enhance the insulin-like and insulin-sensitizing actions of adiponectin have been shown to be effective in improving metabolic abnormalities associated with obesity and diabetes. Interestingly, the insulin-sensitizing effects of exercise have similar metabolic effects as adiponectin in that exercise also promotes glucose uptake into muscle and increases rates of fatty acid oxidation. Recent studies have begun to examine the potential role of adiponectin in mediating the insulin-sensitizing action of exercise by investigating changes in plasma adiponectin levels and tissue-specific adiponectin receptor (AdipoR) expression. In this review, we have summarized the key findings to date which suggest that changes in expression of AdipoR isoforms in skeletal muscle, rather than circulating total adiponectin levels, may be of physiological importance.