Obesity is an independent risk factor for cardiovascular diseases. As the first obese gene product identified, leptin participates in many physiological processes. Besides its well known effects on food intake and energy metabolism, leptin has been shown to regulate cardiovascular function, glucose and lipid metabolism. Although the precise role of leptin on cardiac health is still at large, the peptide may initiate both hypertrophic and anti-hypertrophic effects on hearts. Circulating leptin levels are believed to correlate closely with body mass index (BMI) and total amount of body fat, and predict change of heart morphology and function. This is evidenced by that fact that compromised cardiac function is present in both hyperleptinemic (db/db) and hypoleptinemic (ob/ob) mouse models. Leptin replenishment may reconcile depressed cardiac contractile function in ob/ob mice, indicating the permissive effect of leptin on cardiac function. Multiple signal pathways including NO, Jak/STAT, p38 MAP kinase, ET-1 and NADPH oxidase have been implicated to participate in the cardiac regulatory response of leptin. In addition, elevated plasma leptin levels are speculated to be an independent risk factor for cardiovascular diseases such as hypertension and myocardial infarction. The current dogma indicates that physiological range of leptin may be essential for normal cardiomyocyte structure and function whereas disrupted leptin signaling due to too much or too little leptin may trigger functional and morphological alterations leading to cardiac dysfunction.