During the past 40 years, somatostatin (SST) has been a subject of intensive research. Apart from its substantial role in the neuroendocrine system, due to its dense localization in various areas in the brain, its functions as a neuromodulator have also been thoroughly investigated. Increasing evidence suggests that SST plays a crucial role in memory and cognition. Synthetic forms, biologically active peptide sequences, SST receptor agonists and SST depleting agents have been applied in animal models and in human studies of a number of neuropsychiatric disorders. The translation of experimental data into clinical use could provide novel therapies in neurodegenerative disorders involving cognitive dysfunctions. However in view of the controversial data reported concerning the different roles of the SST receptor subtypes, and the lack of SST analogs that are able to cross diffusion barriers and act selectively at these receptor subtypes, broader clinical use of SST analogs as cognitive enhancers is limited. This review covers the whole range of available experimental results relating to the behavioral effects of SST, and highlights the potential for further investigations.