The Israeli Sand Rat (Psammomys obesus) is an excellent polygenic model for the study of obesity and diabetes. The metabolic characteristics and the heterogeneous development of these defects, including elevated leptin levels, mimic those found in susceptible human populations. Interestingly, only animals that develop metabolic abnormalities demonstrate hyperleptinemia and, in these animals, leptin administration at the same dose that is effective in ob/ob mice is ineffective in reducing food intake or body weight. Perhaps leptin resistance needs to develop in Israeli Sand Rats to allow the development of obesity and, in fact, leptin resistance may be the "thrifty gene" that predisposes individuals to the development of obesity and subsequent metabolic abnormalities. However, there remain many unanswered questions about the physiological actions of leptin. The widespread tissue location of receptors and the actions of leptin independent of food intake highlight the need for further research aimed at determining the major physiological action of this newly discovered and exciting hormone.