The ability to discriminate between pathogenic and non-pathogenic bacteria is extremely important for epithelial cells lining mucosal surfaces and is particularly so in colonic epithelial cells. Accumulating evidence suggests that bacterial recognition systems used by epithelial cells are very different from those in cells of the myeloid lineage and are likely to have developed to maintain mucosal surfaces in a state of homeostasis with the normal microbial flora. Bacterial invasion of epithelial cells or breach of the epithelial barrier provides a signal to epithelial cells to initiate inflammatory responses, which are key events for the clearance of the infecting microbe. Therefore, elucidation of the mechanisms by which epithelial cells recognize bacteria and bacterial products, and of the nature of the innate immune responses that are triggered by these factors are important for our understanding of both the immunology of mucosal surfaces and bacterial pathogenesis.