The endocrine pancreas is composed of islets of Langerhans, which secrete a variety of peptide hormones critical for the maintenance of glucose homeostasis. Insulin is the primary regulator of glucose and its secretion from beta-cells is tightly regulated in response to physiological demands. Direct cell–cell communication within islets is essential for glucose-induced insulin secretion. Emerging data suggest that islet connectivity is also important in the regulating the release of other islet hormones including glucagon and somatostatin. Autocrine and paracrine signals exerted by secreted peptides within the islet also play a key role. A great deal of attention has focused on classical islet peptides, namely insulin, glucagon and somatostatin. Recently, it has become clear that islets also synthesise and secrete a range of non-classical peptides, which regulate beta-cell function and insulin release. The current review summarises the roles of islet cell connectivity and islet peptide-driven autocrine and paracrine signalling in beta-cell function and survival. The potential to harness the paracrine effects of non-classical islet peptides for the treatment of type 2 diabetes is also briefly discussed.