Treatment options for inflammatory bowel disease (IBD) reflect a continuing shift from empiricism to strategies based on improved understanding of the pathophysiology of disease. In susceptible individuals, IBD appears to be the result of defective regulation of mucosal immune interactions with the enteric microflora. This has prompted research directed at the interface of the traditional disciplines of immunology, microbiology, and epithelial cell biology. Whereas immunodiagnostics have been of limited clinical value in IBD, assessments of mucosal rather than systemic immune function are promising. Therapeutically, there is an increasing trend toward more aggressive and earlier use of immunomodulatory agents, particularly for prevention of relapse, with cytokine manipulation as a bridge therapy to achieve remission in patients with acute severe disease. Although most drug treatments are directed toward altering the host response, the rationale for manipulating the enteric flora appears sound and will be the basis of additional future therapeutic strategies. Notwithstanding the widening range of options for drug therapy in IBD, other outcome modifiers and well-established principles of managing chronic disease are as important as ever.