Colorectal cancer is the third and second most common cancer among men and women, respectively, in France. Interest in the chemoprevention of colorectal cancer has increased over the last two decades. Experimental data strongly suggest that ursodeoxycholic acid (UDCA) may have chemopreventative actions in colorectal cancer. UDCA is able to inhibit tumor development in azoxymethane and in dextran-related colitis models. In high-risk populations such as subjects with previous colorectal adenoma removal or inflammatory bowel disease, five out of 10 published studies suggested beneficial effects with UDCA on colonic carcinogenesis. In the azoxymethane model, UDCA inhibited tumor development by counteracting the tumor-promoting effects of secondary bile acids such as deoxycholic acid (DCA). The opposing effects of UDCA and DCA on lipid raft composition may be central to their effects on colonic tumorigenesis. Differential effects of DCA and UDCA on growth factor and inflammatory signals involved in colorectal carcinogenesis, such as epidermal growth factor receptor (EGFR) signaling and COX-2 expression, very likely mediate their opposing effects on colonic tumor promotion and tumor inhibition, respectively.