ATP acts as a humoral mediator to control cell function extracellularly. The receptors that mediate the actions of ATP belong to two classes, the metabotropic P2Y receptors and the transmitter-gated, ion channel P2X receptors. This review describes the structure, distribution, function, and ligand recognition characteristics of P2X receptors, which comprise seven distinct subunits that can function as both homo- and hetero- polymers. The pharmacology of P2X receptors is complicated by marked differences between species orthologues. The current nomenclature is based largely on recombinant receptor studies and detailed knowledge of endogenous P2X receptors in native tissues is limited because of lack of good selective agonists and antagonists for each receptor type.