A brief account of the early history of extracellular signalling by ATP will be followed by a summary of the current subclassification of receptors for purines and pyrimidines. On the basis of cloning, transduction mechanisms and pharmacology, the P1 (adenosine) receptor family has 4 subtypes, while the P2 (ATP, ADP and UTP) receptor family has been divided into P2X ionotropic receptors (7 subtypes) and P2Y metabotropic G protein-coupled receptors (8 subtypes). The distribution of purinoceptors in both neuronal and non-neuronal cells and the physiology and pathophysiology of purinergic signalling will be reviewed. Examples of fast purinergic signalling include cotransmission and neuromodulation, exocrine and endocrine secretion, platelet aggregation, vascular endothelial cell-mediated vasodilatation and nociceptive mechanosensory transduction. Examples of slow (trophic) purinergic signalling include cell proliferation, differentiation and apoptosis in embryological development, neural regeneration, bone resorption, cell turnover of epithelial cells in skin and visceral organs, inflammation, wound healing and cancer. Finally the purinoceptor subtypes expressed on astrocytes, oligodendrocytes, Schwann cells, microglia, Müller cells and enteric glial cells will be summarized as well as evidence for non-lytic release of ATP from glial cells.