Purpose of review: To consider new data and directions coming from experimental models of inflammatory bowel diseases. Recent findings: Advances are discussed in the areas of microbial-host interactions in the intestine, the role of cytokines like IL-23, chemokines like IP-10, and various costimulatory molecules in disease pathogenesis. Multiple regulatory cells have been identified as well as the mechanisms they use to inhibit pathogenic responses to the microbiota in the intestine. New data is available on how the intestine heals after inflammatory insults. Summary: These data are providing fundamental insights into the pathogenesis of IBD and thus are forming the basis of new therapeutic approaches, many of which will be translated to the clinic in the near future. © 2004 Lippincott Williams & Wilkins.