In seeking to answer this question, we and others have focused on the innate immune receptors that are present on the mucosa, and have examined the response of these receptors to known ligands in the development of mucosal inflammatory disorders. Such ligands may be broadly grouped into two categories: the so called "danger signals," a term used by Matzinger (24) , also called damage-associated molecular patterns (DAMPs) ( [25, 26] provide recent reviews); and those ligands on the surface or interior of pathogen-associated molecular patterns (PAMPs) ( Table 2) . Not surprisingly, there is a great deal of interest in identifying the important receptors for DAMPs and PAMPs expressed by various cell types, so as to accurately define their relative role in the development of inflammation. In this regard, several investigators have established that DAMPs and PAMPs are recognized by TLRs in many cells, including epithelial cells: a list of the TLRs and their cognate ligands appears in Table 1 . Although current dogma suggests that circulating leukocytes play a central role in the coordination of the immune response, emerging evidence suggests that the epithelium also plays a key role in the recognition and response to various "danger molecules" (27) (28) (29) (30) (31) . This review will examine in detail the various roles of epithelial signaling via TLRs in the development of common, and often devastating, mucosal inflammatory conditions. Much of the focus will be on the TLR-initiated signaling in response to PAMPs, as the majority of work has been performed in this area.