Our general mission is to understand how tissue damage causes the body to mount an inflammatory response. Over the last decade, a new hypothesis of how our bodies respond to tissue damage or pathogenic invasion has taken place. The current prevailing hypothesis is that an inflammatory response does not occur solely in response to foreign or nonself molecules but, rather, in response to self molecules released from damaged tissue. The self molecules responsible for mounting an inflammatory response have not been conclusively identified, although it is speculated that they must have the following features: 1) they should be easily and quickly generated in the extracellular space, probably by release from an existing intracellular pool, 2) under resting conditions their extracellular concentration should be close to zero to allow a high signal-to-noise ratio upon release, 3) they should be highly mobile in the pericellular environment, 4) they should be recognized by specific receptors expressed in immune cells, and 5) they should be easily destroyed once they reach the extracellular space. Since nucleotides meet all these criteria, these molecules and their cell surface receptors (P2 receptors) have emerged as key players in the process of inflammation.