Although the effects of nucleotides in the cardiovascular system have been known for almost 70 years, it is only in the past few years that some of the P2 receptors at which they act have been cloned and characterized. It is now clear that the control of cardiovascular function by nucleotides is complex, involving multiple receptors and multiple effects in the different cell types of importance. In this review Mike Boarder and Susanna Hourani summarize the P2 receptors that are present in endothelial cells, platelets, smooth muscle and nerves, the signalling pathways that they activate and the responses that are produced. They also discuss the important role of nucleotides in the interactions between the different cell types, and the implications of this in vascular disease.