This review discusses the current progress in the understanding of how commensal-mediated activation of toll-like receptors (TLRs) may be involved in the regulation of physiological and pathophysiological processes of the intestinal mucosa including tissue regeneration and inflammation. While regulation of TLRs and their downstream signaling mediators might be used to prevent and treat inflammatory bowel diseases, paradoxically, at this time, it remains uncertain whether this would be more effectively accomplished by enhancing or inhibiting these pathways.