The causes of inflammatory bowel disease remain uncertain, but increasing evidence supports roles for two pathogenic processes: genetic susceptibility in the host and an aberrant host response to enteric bacteria. Here, we review studies showing that the pathogenesis of inflammatory bowel disease involves both bacterial agents and genetic susceptibilities. We discuss the roles of known and novel commensal intestinal bacteria in the pathogenesis of inflammatory bowel disease and the various recombinant approaches used to identify these pathogens.