Adiponectin is a protein hormone produced exclusively by adipocytes. Its circulating levels are decreased in individuals with obesity, atherosclerosis and insulin resistance, suggesting that its deficiency may have a causal role in the etiopathogenesis of these diseases. Studies have shown that adiponectin administration in rodents has insulin-sensitizing, anti-atherogenic and anti-inflammatory effects and under certain settings also decreases body weight. Therefore, adiponectin replacement in humans may represent a promising approach to prevent and/or treat obesity, insulin resistance and type 2 diabetes; however, clinical studies with adiponectin administration need to be conducted to confirm this hypothesis. Current experimental and clinical data regarding adiponectin physiology and pathophysiology are detailed in this review.