Nesfatin-1 is a recently identified 82-amino-acid peptide derived from the precursor protein, nucleobindin2 (NUCB2). The brain distribution of NUCB2/nesfatin-1 at the mRNA and protein level along with functional studies in rodents support a role for NUCB2/nesfatin-1 as a novel satiety molecule acting through leptin-independent mechanisms. In addition, nesfatin-1 induces a wide spectrum of central actions to stimulate the pituitary-adrenal axis and sympathetic nervous system and influences visceral functions and emotion. These central actions combined with the activation of NUCB2/nesfatin-1 neurons in the brain by various stressors are indicative of a role in the adaptive response under stressful conditions. In the periphery, evidence is mounting that nesfatin-1 exerts a direct glucose-dependent insulinotropic action on β-cells of the pancreatic islets. However, the cellular mechanisms of nesfatin-1's action remain poorly understood, partly because the receptor through which nesfatin-1 exerts its pleiotropic actions is yet to be identified.