The obese gene product, leptin, plays a central role in food intake and energy metabolism. The physiological roles of leptin in human bodily function have been broadened over the past decade since leptin was first discovered in 1994. Evidence has suggested that leptin plays a specific role in the intricate cascade of cardiovascular events, in addition to its well-established metabolic effects. Leptin, a hormone linking adiposity and central nervous circuits to reduce appetite and enhance energy expenditure, has been shown to increase overall sympathetic nerve activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin is capable of regulating cardiac and vascular contractility through a local nitric oxide-dependent mechanism. However, elevated plasma leptin levels or hyperleptinemia, have been demonstrated to correlate with hyperphagia, insulin resistance and other markers of the metabolic syndrome including obesity, hyperlipidemia and hypertension, independent of total adiposity. Elevated plasma leptin levels may be an independent risk factor for the development of cardiovascular disease. Although mechanisms leading to hyperleptinemia have not been well described, factors such as increased food intake and insulin resistance have been shown to rapidly enhance plasma leptin levels and subsequently tissue leptin resistance. These findings have prompted the speculation that leptin in the physiological range may serve as a physiological regulator of cardiovascular function whereas elevated plasma leptin levels may act as a pathophysiological trigger and/or marker for cardiovascular diseases due to tissue leptin resistance.