P2X receptors are cation-selective ion channels activated by extracellular ATP. They form homo- and heterotrimeric complexes that differ in their functional properties and subcellular localization. These membrane ion channels are also expressed in pulmonary epithelial cells. Recent work indicates that alveolar epithelial type I cells selectively express P2X(4) and P2X(7) receptor subtypes in addition to a large number of other ion channels present in the alveolar epithelium. Up- or downregulation of their expression is associated with several disease states. This minireview analyses the role of P2X receptors and of extracellular ATP and adenosine in lung disease, the relationship of P2X receptors to other ion channels in the alveolar epithelium and their distribution in lipid rafts/caveolae.