The talk will begin with a description of the discovery in the early 1970’s of purinergic neurotransmission (i.e. ATP acting as a neurotransmitter) and the struggle we had for the next 20 years to establish this hypothesis. It is now recognised that the purinergic signalling system is one of the most ancient and widespread intercellular signalling systems in living tissue. The major conceptual steps leading to our current understanding of purinergic signalling will be described, including ATP as a cotransmitter, cloning and characterisation of P1 (adenosine), P2X (ATP) ion channel and P2Y (ATP, ADP, UTP, UDP) G protein-coupled receptors, physiological release of ATP by mechanical deformation of cells, identification of ectonucleotidases and both fast and long-term (trophic) purinergic signalling. Reference will be made to some of the key scientists who have influenced its development. Finally, some of the exciting areas of current interest will be considered, including in particular the pathophysiology of purinergic signalling and its therapeutic potential.