--- - |2 Abstract The exact physiological role for the monoamine serotonin (5‐HT) in modulation of insulin secretion is yet to be fully understood. Although the presence of this monoamine in islets of Langerhans is well established, it is only with recent advances that the complex signalling network in islets involving 5‐HT is being unravelled. With more than fourteen different 5‐HT receptors expressed in human islets and receptor‐independent mechanisms in insulin‐producing β‐cells, our understanding of 5‐HT's regulation of insulin secretion is increasing. It is now widely accepted that failure of the pancreatic β‐cell to release sufficient amounts of insulin is the main cause of type 2 diabetes (T2D), an ongoing global epidemic. In this context, 5‐HT signalling may be of importance. In fact, 5‐HT may serve an essential role in regulating the release of insulin and glucagon, the two main hormones that control glucose and lipid homoeostasis. In this review, we will discuss past and current understanding of 5‐HT's role in the endocrine pancreas. - 'Acta Physiologica, EarlyView. '