In summary, many experimental models of IBD have been generated in the past decade using genetic manipulation. The new experimental models can be placed into several major categories based on probable pathogenic mechanisms. These models have affirmed the major working hypothesis of IBD pathogenesis, that it is due to a dysregulated immune response to the enteric bacterial flora (or members thereof) in a genetically susceptible host. Insights gained from these experimental models will likely translate into new forms of therapy for patients in this coming decade. © 2004 Lippincott Williams & Wilkins.