The beneficial effect of intravenous immunoglobulin (IVIg) in certain autoimmune disorders has led to the development of clinical trials in a large number of autoimmune and systemic inflammatory diseases. Experimental studies are being carried out to understand better the mechanisms of action of IVIg. In this review, we discuss the clinical use of IVIg in autoimmune disorders and outline the possible mechanisms by which IVIg may be exerting an immunoregulatory effect in various autoimmune and systemic inflammatory diseases. A clear understanding of the mechanisms of action of IVIg in autoimmune diseases will facilitate the optimization of their use as a therapeutic alternative to conventional immunosuppression.