Intravenous immunoglobulin (IVIg) is increasingly being used in the treatment of a wide range of autoimmune and systemic inflammatory diseases involving distinct pathogenesis. However, the mechanism by which IVIg exerts its sustained therapeutic effects in these diverse diseases has remained enigmatic. Recent findings from experimental and clinical research have, however, provided new insights into the mechanisms of action of IVIg. IVIg targets various cellular (such as dendritic cells, macrophages, monocytes, B and T cells) and soluble compartments (cytokines, complements, autoantibodies and autoantigens) of the immune system that are involved in the pathogenesis of autoimmune diseases. Thus, the mechanisms of actions of IVIg are mutually non-exclusive and work in synergy to contribute to its therapeutic effects. © 2009 Elsevier Ltd. All rights reserved.