AbstractPurines appear to be the most primitive and widespread chemical messengers in all kingdoms of the Domain Eucarya. There is evidence for purinergic signaling in plants, invertebrates, and lower vertebrates from protozoa to birds. Much is based on pharmacological studies, but important recent papers have utilized the techniques of molecular biology, and ATP‐gated ion channels (ionotropic purinoceptors) have been cloned and characterized in primitive invertebrates, including the social amoebaDictyosteliumand the platyhelminthSchistosoma, as well as the green algaeOstreococcus. These ancient purinoceptors resemble P2X receptors identified in mammals. This suggests that contrary to earlier speculations, P2X ion channel receptors appeared early in evolution, while G protein‐coupled P1 and P2Y receptors were introduced either at the same time or perhaps even later. The absence of gene coding for P2X receptors in some animal groups (e.g., in some insects, roundwormCaenorhabditis elegans, and the plantArabidopsis), in contrast to the potent pharmacological actions of nucleotides in the same species, suggests that novel receptors are still to be discovered.WIREs Membr Transp Signal2012, 1:188–200. doi: 10.1002/wmts.13For further resources related to this article, please visit theWIREs website.