Immunomodulators are a class of drugs that attenuate the underlying inflammatory processes of Crohn's disease (CD) and ulcerative colitis (UC), the two major inflammatory bowel diseases (IBD). These agents play a prominent role in the management of refractory and steroid-dependent IBD. The immunomodulatory drugs in the IBD arsenal include azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, and tacrolimus. Azathioprine and 6-mercaptopurine are considered first-line immunosuppressants due to their proven efficacy in both CD and UC and their safety profile, whereas cyclosporine occupies a niche as a surgery-sparing agent in the acute management of severe, steroid-refractory UC. Immunomodulators also appear to have a role as adjunctive therapy when used with infliximab or other biologic agents to reduce immunogenicity. Although data have been limited to observational studies, azathioprine and 6-mercaptopurine may be used during pregnancy.