The immunology of inflammatory bowel disease continues to be an intense area of investigation for clues to the pathogenesis of Crohn disease and ulcerative colitis. As typical with complex diseases, inflammatory bowel disease research is continuously evolving. Without abandoning traditional areas of study, such as humoral and cellular immunity and cytokines, investigation is broadening to explore new molecules and biologic phenomena. Novel cytokines and cell adhesion molecules appear to be involved in inflammation, while the role of nitric oxide is being clarified. Leukocyte resistance to apoptosis appears to be a major contributing factor to Crohn disease. Epithelial cell-derived defensins and receptors are arising as key molecules mediating the interaction of innate and acquired mucosal immunity with the enteric flora, and explaining how the latter participates in gut inflammation. The results of these combined studies are opening novel therapeutic horizons whose implementation offers better forms of treatment.