Although systemic corticosteroids are often successfully applied for induction of clinical response and remission of inflammatory bowel disease (IBD) patients presenting with a flare, a proportion of these treated patients present with a primary non-response to steroids, resistance or steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided given the high frequency of adverse treatment effects. This article highlights the indications for the use of immunomodulators (e.g. azathioprine, 6-mercaptopurine and methotrexate), drugs directed against tumor necrosis factor (anti-TNF) as well as calcineurin inhibitors (e.g. cyclosporine and tacrolimus).