This review summarizes the recent findings on the localization of somatostatin (SRIF)-related peptides in local circuit interneurons and long projection neurons. These differential locations are discussed in relation to the multiple roles of SRIF 14 and SRIF 28 in neuroendocrine and autonomic regulation. The coexistence of SRIF with other neuropeptides and neurotransmitters, including nitric oxide, is described. The pharmacological and functional properties of the recently cloned family of SRIF receptor subtypes are reviewed as well as their localization. Finally, the decrease in SRIF concentrations in the cerebrospinal fluid (CSF) and the central nervous system (CNS) commonly associated with Alzheimer's disease is critically evaluated.