Management of Crohn's disease has changed considerably in recent years. The discovery of tumor necrosis factor (TNF) as a pivotal cytokine in the inflammatory cascade has led to the development of several neutralizing antibodies, soluble receptors, and small molecules, interfering with TNF gene transcription and expression. Infliximab is the only monoclonal antibody that is commercially available. This potent molecule is effective for both active and fistulizing disease in the acute and maintenance phases of treatment. In addition to anti-TNF agents, weekly methotrexate injection and the classic "antimetabolites" azathioprine and 6-mercaptopurine remain highly valuable as maintenance drugs. "Tailored" antimetabolite therapy has now become possible with metabolite measurements and determination of the TPMT gene. The active metabolite thioguanine itself could be a promising alternative in patients who are intolerant of 6-mercaptopurine. In fistulizing disease, infliximab is becoming the treatment of choice, although fistula tracks do not disappear permanently and many patients still need surgical intervention.