Short- and long-term anti tumor necrosis factor-alpha (TNF-alpha) therapy in Crohn's disease is generally well tolerated. However, clinicians must be vigilant for the occurrence of infrequent but serious events. Antibodies to infliximab interfere with the safety and efficacy of the drug and may lead to infusion reactions, loss of response, and delayed serum sickness-like reactions. The optimal strategy to overcome the production of antibodies is systematic maintenance treatment. The most effective way to minimize the risk of opportunistic infection is to vaccinate the patients and to avoid the use of corticosteroids. All patients should receive varicella vaccination, annual influenza vaccination (also pandemic influenza A - H1N1), and pneumococcal vaccination every 3 to 5 years. In addition, HPV vaccine should be administered to young females, and hepatitis B vaccine to HBV seronegative patients. Unlike corticosteroids, infliximab does not pose an increased risk for serious infection. Treatment with anti TNF-alpha agents increases the risk of activation of latent TB. Therefore, all patients should be screened for TB infection before starting with therapy. The use of anti TNF-alpha agents in combination with immunomodulators is associated with an increased risk of non-Hodgkin's lymphoma, but the absolute rate remains low. There is no evidence that other malignancies and death rates in patients treated with anti TNF-alpha strategies are increased. Reported data from 300 pregnant women treated with infliximab have not shown any untoward effects of treatment on pregnancy outcome.