Nucleotides such as ATP and ADP act as intercellular messengers and exert a widespread influence on cellular function by acting on a variety of cell surface receptors. Until recently, progress has been restrained, in part, by a lack of cloned receptors. Now, however, the successful cloning of a variety of P2 purinoceptors is holding out the prospect of rapid advances in the understanding of this diverse group of receptors and the potent therapeutic resource they represent. In this article, Michael Boarder and colleagues summarize the findings of recent cloning studies, and assess the impact of these on the understanding of the function of the G protein-coupled P2 purinoceptors in several types of cells and tissues.