Due to intensive research in the field of cytokines during the last decade the knowledge of cytokine mediated processes has increased intensively. Modulation or even inhibition of the inflammatory cascade gave hope to effective therapeutic possibilities in sepsis or autoimmune diseases, particularly in rheumatoid arthritis (RA). Interestingly the application of biological immunomodulating substances could not increase the prognosis in sepsis, sometimes even deterioration occurred. However, in inflammatory bowel diseases and RA substantial efficacy could be revealed. Since blockade of II-1 or II-2 led to some beneficial results, but also sometimes to significant toxicity, TNF-alpha blockade gave hope to constitute a promising therapeutical target. Since the efficacy of a monoclonal anti-TNF-alpha antibody and a recombinant soluble TNF receptor p75 fusion protein had been demonstrated in animal studies and in vitro, these results could be confirmed in controlled multicenter trials, showing significant improvement of patients according to Paulus and/or ACR criteria. However, a final assessment of therapeutical TNF-alpha blockade in RA cannot be given yet, since the tolerability in long-term application, particularly with respect to the risk of infections and the induction of malignancies and antibodies (e.g. drug induced lupus erythematosus) has to be observed carefully for longer times. Also the cost effectiveness of this new therapeutic approach needs further investigations.