In mammalian brain, the somatostatin (SRIF: somatotropin release-inhibiting factor) family is composed of two peptides: SRIF and cortistatin (CST), which interact with five different receptor subtypes, sst(1-5). This review summarizes the properties of these receptors, the involvement of somatostatinergic systems in Alzheimer's disease (SRIF/acetylcholine (Ach), SRIF/amyloid beta peptides, and SRIF/tau interactions) and their role in cognition from early studies using cysteamine as an SRIF depleting substance to the use of subtype selective analogues and knockout mice, and modulation of synaptic plasticity. The current SRIF story illustrates how cognition and emotion are intimately integrated in brain function.