The vgf gene (non-acronymic) is highly conserved and was identified based on its rapid induction in vitro by nerve growth factor, although subsequently this can be induced by brain-derived neurotrophic factor, and glial derived growth factor. The vgf gene gives rise to a 68kDa precursor polypeptide, which is robustly, relatively selectively and is synthesized exclusively in neuronal and neuroendocrine cells. Post-translational processing by neuroendocrine specific prohormone convertases in these cells results in the production of a number of smaller peptides. The vgf gene and peptides are widely expressed through the brain particularly in the hypothalamus and hippocampus and are associated with a number of neuroendocrine roles. Here, we will review the roles of VGF gene and its peptides in the regulation of energy expenditure and beyond.