Purinergic receptors, represented by several families, are arguably the most abundant receptors in living organisms and appeared early in evolution. After slow acceptance, purinergic signalling in both peripheral and central nervous systems is a rapidly expanding field. Here, we emphasize purinergic co-transmission, mechanisms of release and breakdown of ATP, ion channel and G-protein-coupled-receptor subtypes for purines and pyrimidines, the role of purines and pyrimidines in neuron-glial communication and interactions of this system with other transmitter systems. We also highlight recent data involving purinergic signalling in pathological conditions, including pain, trauma, ischaemia, epilepsy, migraine, psychiatric disorders and drug addiction, which we expect will lead to the development of therapeutic strategies for these disorders with novel mechanisms of action.