There is now renewed interest in the role of antibodies in autoimmunity. Recent compelling evidence indicates that autoantibodies and the effector mechanisms they induce, for example, Fc receptor activation of leukocytes and/or the complement cascade, are central players in the development of autoimmunity, by perpetuating inflammation and perhaps even regulating the process itself. Of increasing interest are Fc receptors, which have been more closely investigated in the past decade using recombinant proteins, gene deficient mice and mouse models of human disease. These analyses point towards major roles of Fc receptors in antibody hypersensitivity reactions and by extension autoimmune disease, and they reveal opportunities in the development of novel therapeutic approaches in the treatment of autoimmune diseases.