The gastrointestinal tract is vital to food digestion and nutrient absorption as well as normal salt and water homeostasis. Studies over the last several years have shown that the Ca2+-sensing receptor is expressed along the entire gastrointestinal tract. The potential roles for the receptor in gastrointestinal biology are now only beginning to be elucidated and much work remains. Well-studied physiological effects include regulation of gastric acid secretion and modulation of fluid transport in the colon. It remains to be determined if the Ca2+-sensing receptor is involved in calcium handling by the gastrointestinal tract. The ability of organic nutrient receptor agonists/allosteric modifiers, such as polyamines and L-amino acids, to activate the Ca2+-sensing receptor suggest potential roles in signalling nutrient availability to gastric and intestinal epithelial cells. In addition, polyamines are crucial for normal cell proliferation and differentiation required to sustain the rapid turnover of gastrointestinal epithelial cells and the Ca2+-sensing receptor may be involved in this function. Activation of the colonic Ca2+-sensing receptor can abrogate cyclic nucleotide-mediated fluid secretion suggesting a role for the receptor in modifying secretory diarrheas like cholera. Finally, the Ca2+-sensing receptor has been suggested to provide a mechanism for the effect of calcium intake in reducing the risk of colon cancer.