The introduction of immunomodulator therapy in the treatment of patients with inflammatory bowel disease (IBD) has provided an important tool in modifying the mucosal immune system thought to be important in the pathogenesis of IBD. Currently available immunomodulating agents include azathioprine, 6-mercaptopurine, cyclosporin, and methotrexate. Recent clinical trials have demonstrated that these agents have an important therapeutic role in the treatment of patients who are either refractory or intolerant to traditional medical therapy. They are useful in the induction and maintenance of remission for both ulcerative colitis and Crohn's disease. However, these agents have significant toxicities and limited efficacy. In addition, potential risks of malignancy and infection limit their indiscriminate use. Thus, with the better understanding of the molecular basis of mucosal immunity, innovative immune-modifying therapies, such as antagonists of cytokines and inhibitors of T-cell activation, are being developed. It is likely that these exciting developments will soon result in specific immune modulating therapy with improved efficacy and reduced toxicity in the treatment of patients with IBD.