Mucosal surfaces are colonized by a complex microbiota that provides beneficial functions under normal physiological conditions, but is capable of contributing to chronic inflammatory disease in susceptible individuals. Of the mucosal tissues, the mammalian intestine harbors an especially high number of microbes with a remarkable diversity. Inflammatory bowel disease (IBD) is a group of chronic relapsing inflammatory disorders of the intestinal mucosa. Evidence from human studies and animal models provides compelling support that intestinal microbes play a key role in disease pathogenesis. While the existence a specific causative pathogen is possible, it appears more likely that intestinal microbes normally present as commensal microbiota may trigger inflammation and perpetuate disease in genetically susceptible individuals. There may be also a shift in the makeup of the commensal flora to a nonphysiologic composition that is more prone to disease (termed dysbiosis). Evidence supports that genetic susceptibility stems from one or more defects in mucosal immune functions, including microbe recognition, barrier function, intercellular communication and antimicrobial effector mechanisms. It is quite plausible to imagine that the chronic inflammation of IBD may in some cases be a normal immune response to an abnormal adherent invasive microbiota and in other cases an over exuberant immune response to an otherwise normal commensal microbiota.