The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In β cells, stimulation of P2Y₁ receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y₁ receptors, there is also evidence for other P2 and adenosine receptors in β cells (P2Y₂, P2Y₄, P2Y₆, P2X subtypes and A₁ receptors) and in glucagon-secreting α cells (P2X₇, A₂ receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y₂, P2Y₄, P2Y₁₁, P2X₄ and P2X₇ receptors could regulate secretion, primarily by affecting Cl⁻ and K⁺ channels and intracellular Ca²⁺ signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases.