Somatostatin (SST) regulates multiple biological processes via five genetically distinct, G-protein coupled receptors. Clinical interest in therapy for neuroendocrine and metabolic disorders has resulted in the development of new tools for exploring the function of somatostatin receptors (SSTRs). The development of highly SSTR-selective agonists and antagonists, animal models with the deletion of individual SSTRs, as well as SSTR-specific antibodies have all been utilized in delineating SSTR functions. In the pancreas, SST is a potent regulator of insulin and glucagon secretion. Indeed, the inappropriate regulation of pancreatic A- and B-cell function in metabolic diseases provides an impetus to evaluate the SSTRs as therapeutic targets. By combining the results obtained from molecular biology, pharmacology and immunochemical studies the current review provides a summary of important recent developments which have extended our knowledge of SST actions in the endocrine pancreas.