Bile acids, an end-product of cholesterol catabolism, are synthesized in the liver, stored in the gallbladder, and secreted into the duodenum in response to a meal to allow the absorption of dietary lipids and fat-soluble vitamins. Epidemiological studies have shown a correlation between high levels of intestinal bile acids and colorectal cancer progression. In this study, Modica and colleagues have investigated the role of the Farnesoid X Receptor (FXR), the transcriptional mediator of the physiological effects of bile acid, in the context of intestinal tumorigenesis. First, the authors demonstrate that FXR expression is dramatically reduced in human and mouse intestinal neoplasia. Second, they provide evidence that the reduced expression of FXR in the intestine further promotes inflammation and tumor progression in mouse models. Finally, using in vivo and in vitro studies, the authors suggest a protective role of FXR in intestinal tumorigenesis via induction of apoptosis and propose therapies aimed at reactivating FXR for the management of colorectal cancer. For details, see the article by Modica and colleagues on page 9589 of this issue.