Abstract The term neuropeptides commonly refers to a relatively large number of biologically active molecules that have been localized to discrete cell populations of central and peripheral neurons. I review here the most important histological and functional findings on neuropeptide distribution in the central nervous system (CNS), in relation to their role in the exchange of information between the nerve cells. Under this perspective, peptide costorage (presence of two or more peptides within the same subcellular compartment) and coexistence (concurrent presence of peptides and other messenger molecules within single nerve cells) are discussed in detail. In particular, the subcellular site(s) of storage and sorting mechanisms within neurons are thoroughly examined in the view of the mode of release and action of neuropeptides as neuronal messengers. Moreover, the relationship of neuropeptides and other molecules implicated in neural transmission is discussed in functional terms, also referring to the interactions with novel unconventional transmitters and trophic factors. Finally, a brief account is given on the presence of neuropeptides in glial cells.