Therapeutic polyclonal intravenous immunoglobulin (IVIg) consists of normal IgG obtained from the pools of plasma of several thousand healthy blood donors. IVIg is used as substitutive treatment of primary and secondary immunodeficiences. Since the first study of Paul Imbach who demonstrated the beneficial effect in idiopathic thrombocytopenic purpura, IVIg is also used in a number of autoimmune and inflammatory diseases. The immunoregulatory effects of IVIg in autoimmune diseases depend on the interaction of Fc portion of immunoglobulins with Fc receptors and on the selection of lymphocyte repertoires of patients through variable regions of infused immunoglobulins. IVIg modulates the activation and effector functions of B and T lymphocytes, neutralizes pathogenic autoantibodies, interferes with antigen presentation and has a strong anti-inflammatory effect which depends on its interaction with the complement system, cytokines and endothelial cells. The immunomodulatory potential of IVIg in patients is thus a result of a variety of complex mechanisms that act in a synergy.