Substantial progress in our understanding of molecular and cellular biology has allowed us to design biological therapeutics ('biologicals') with defined targets and effector functions. Various biologicals aimed at interfering with critical steps of inflammation have been employed in an attempt to silence chronic unwanted immune responses, as are characteristic of autoimmune diseases. These biologicals have greatly contributed to our current knowledge of pathogenetic mechanisms in autoimmune diseases. However, although some of the biologicals have been extremely successful in treating the symptoms of chronic inflammation, biological therapy has not yet met the expectation of permanently silencing chronic immune responses. Current concepts and future directions of biological therapy, with a focus on immunosuppression as a treatment of human autoimmune diseases, are discussed.