Purinergic receptors are expressed widely in the gastrointestinal (GI) tract and liver and serve a variety of functions from acting as neutrotransmitters, to autocoid and paracrine signaling, to cell activation and immune response. ATP and UTP are released by many cell types in response to specific physiological signals. Consequently, low concentrations of nucleotides and nucleosides are present in blood, bile, and interstitial fluids under normal conditions. However, during inflammation ATP levels in the vicinity of the cell rises rapidly. It is estimated that up to 1% of intracellular ATP can be released in response to stimuli. Given that intracellular ATP is around 3-6 mM, such an increase is highly consequential in the kinetics of the P2 receptor. Importantly, ATP is rapidly metabolized into adenosine by ectonucleotidases and adenosine in turn acts on the P1 receptor to elicit additional cellular responses. In this article, the distribution of purinergic receptors, P1 and P2, in the gastrointestinal tract and their physiological and pathophysiological role will be reviewed.