Obesity is a heterogeneous pathologic condition that is driven by interactions between multiple genetic and environmental factors. The discovery of leptin has provided the useful clue to the molecular dissection of central pathways involved in the regulation of food intake and body weight. Monogenic obesity in human has been documented. Several obesity causing genes within the leptin-POMC-melanocortin axis have been identified: Leptin, leptin receptor, proopiomelanocortin (POMC), prohormone convertase 1 (PC1), and melanocortin receptor-4 (MC4-R) genes. The patients who have a mutation of such genes developed early onset of obesity and distinct metabolic abnormalities. Also, several gene mutations have been identified in some syndromes presenting hereditary symptomatic obesity.