Obesity is associated with increased risk of many diseases, inluding diabetes, heart attack, hypertension, cancer and even in early death. Identification of the association between weight gain and hypothalamic functions with respect to hormonal effects will provide a better understanding of obesity. Nesfatin-1, derived from NEFA/nucleobindin2 (NUCB2), is a recently introduced hormone that suppresses food intake via melanocortin system in hypothalamus. Nesfatin-1 administration, through intracerebroventricular, subcutaneous or intraperitoneal injections or even by nasal sprey, inhibited appetite from 3 to 14 hours. In addition, it reduces weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. Due to these effetcs on energy metabolism homeostasis, nesfatin-1 could play an important role in protection against the development of obesity. In recent years, there is a great progress on the detection of localization of nesfatin-1 in the brain and peripheral tissues. In future studies, to understand the anorexic effect of nesfatin-1 the important molecular mechanisms related with the nesfatin-1 receptor and the regulation of NUCB2 processing and nesfatin-1 release should be clearly defined. In the light of recent studies, nesfatin-1 may be termed as a new and promising anti-obesity drug that can be used in the near future.