The neuropeptide Y family of peptides consists of neuropeptide Y (NPY), which is expressed in the central and peripheral nervous systems, and peptide YY (PYY) and pancreatic polypeptide (PP) which are gut endocrine peptides. All three peptides are 36 amino acids long and act on G-protein-coupled receptors. NPY and PYY are present in all vertebrates, whereas PP probably arose as a copy of PYY in an early tetrapod ancestor. NPY is one of the most conserved peptides during evolution and no gnathostome (jawed) species differs from the ancestral gnathostome sequence at more than five positions. PYY is more variable, particularly in mammals which have nine differences to the gnathostome ancestor. PP may be the most rapidly evolving neuroendocrine peptide among tetrapods with only 50% identity between mammals, birds, and amphibians. Ancestral gnathostome NPY and PYY seem to have differed at only four positions, suggesting that the gene duplication occurred shortly before the appearance of the gnathostomes. The two peptides differ from one another at 9-12 positions in tetrapod species and share at least two receptor subtypes in mammals. In bony and cartilaginous fishes, NPY and PYY have only 5-6 differences which, together with more extensive neuronal localization of PYY, indicate an even greater functional overlap between the two peptides in these animal groups. The emergence of sequence information for several receptor subtypes from various species will shed additional light on the evolution of the functions of the NPY-family peptides.