We discovered a new anorexigenic protein, nesfatin/nucleobindin-2 (NUCB2), which includes an EF-hand, calcium-binding motif. Nesfatin/NUCB2 is converted to nesfatin-1, which may be a physiologically active form in the body. Centrally and systemically administered nesfatin-1 inhibits appetite and body weight gain in rodents. The mid-segment of nesfatin-1 appears to be important in the inhibition of food intake. Intranasal administration of the mid-segment inhibits appetite. Nesfatin-1 may also be involved in the regulation of gastrointestinal function and insulin secretion. We have summarized the recent progress in the research of nesfatin-1.