Nesfatin-1, a food-intake inhibiting factor processed from nucleobindin 2 (NUCB2), was originally identified by the Oh-I research group. The initial functional studies on NUCB2/nesfatin-1 were mainly focused on its properties of appetite regulation. As is well known, emotional state has an interactional relationship with food intake, and difficulties in regulating emotion and stress have a great influence on appetite and body weight. Some anorexigenic or orexigenic neurotransmitters also play a role in the adjustment of emotion and stress responses in addition to their actions on the homeostatic regulation of food intake, including neuropeptide Y (NPY), melanocyte stimulating hormone (MSH), corticotropin-releasing factor (CRF), and ghrelin. Furthermore, NUCB2/nesfatin-1 immunoreactive neurons were detected extensively in brain areas involved in emotion and stress regulation, such as the hippocampus, hypothalamus, amygdala, and prefrontal cortex (PFC). These data suggest that NUCB2/nesfatin-1 might also have effects on affective states; therefore, many studies were carried out researching the functions of NUCB2/nesfatin-1 in emotion regulation. An increasing body of evidence has been published to elucidate the stress-related activation of NUCB2/nesfatin-1 neurons and alteration of NUCB2/nesfatin-1 concentrations, as well as the behavioral changes induced by the administration of NUCB2/nesfatin-1. In the present review, we summarized current data focusing on the association between NUCB2/nesfatin-1, stress, and psychiatric disorders to elucidate the functions of NUCB2/nesfatin-1 in emotion regulation.