The approach of targeting cytokines has dramatically improved the success in the treatment of rheumatoid arthritis (RA). The blocking of tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 is well established in clinical practice, but a lack or loss of clinical response still occurs in up to 30% of RA patients. Therefore, enhanced efforts must be made to develop new strategies to disrupt the inflammatory process and to inhibit synovitis and joint destruction. In this respect, the blocking of IL-6 receptor with tocilizumab, the prevention of costimulatory T cell signals by abatacept, or targeting B cells with rituximab look promising in clinical trials. Furthermore, blocking intracellular signal transduction broadens the spectrum of targeted therapy. This article reviews recent clinical aspects of established anti-cytokine therapies and gives an insight into the experimental and clinical development of new specifically acting drugs.