Therapeutic antibodies against TNF-alpha are an important therapeutic innovation in recent years in treating complicated Crohn's disease. Chimeric infliximab fully human produced Adalimumab and Certolizumab-Pegol, a humanized, PEGylated anti-TNF-alpha antibody Fab'fragment, are therapeutic antibodies against TNF. All three antibodies have a rapid onset of action, with two thirds of the patients with refractory Crohn's disease showing an initial clinical response to the anti-TNFalpha treatment and only 20-30 % develops a lasting remission. Clinical benefits include closure of draining fistulas and reduction of chronic glucocorticoid medication. When considering an anti TNF-alpha therapy a long term strategy is needed and a systematic maintenance treatment should be developed. The antibodies recognize different epitopes but have a complementary mode of action. Does one antibody fail, especially after an initial clinical response, a second antibody can still show an effect. More recent anti TNF-alpha antibodies can be applied without an azathioprine comedication. Severe side effects like an increase risk of infection and malignancies are a class effect and closely linked to the mode of action. When patients are properly selected, the clinical benefit outweighs the side effects. Before starting an immunosuppressive therapy or an anti-TNF-alpha therapy screening for latent tuberculosis is mandatory. An abscess has to be excluded. Due to the high risk of infection any symptoms which might be a sign of complications during therapy should result in a thorough diagnostic examination. Patients should be documented in registries.