Nesfatin/nucleobindin 2 (NUCB2) is expressed in the appetite-control hypothalamic nuclei and brainstem nuclei. Nesfatin/NUCB2 expression in the paraventricular nucleus of the hypothalamus was modulated by starvation and refeeding. Intracerebroventricular administration of nesfatin-1 dose-dependently inhibited food intake for 6 hours in male Wistar and leptin resistant, Zucker fatty rats. Intraperitoneal administration of nesfatin-1 and its mid-segment (M30) dosedependentlyinhibited food intake for 3 hours in male ICR mice. Intraperitoneal administration of M30 also decreased foodintake in leptin-resistant, genetically obese (ob/ob), diabetic (db/db) mice and mice fed a 45% high fat diet for 28 days. Intraperitoneal administration of M30 increased proopiomelanocortin and cocaine- and amphetamine- related peptide mRNA expression in the nucleus of the solitary tract of mice. In addition, intranasal administration of nesfatin-1 significantly inhibited food intake for 6 hours in male Wistar rats. We summarize recent observations about nesfatin-1, and attempt to present future direction of nesfatin-1 research for developing a new anti-obesity treatment.