The immunoregulatory and anti-infective properties of normal circulating polyclonal Abs have been exploited for the therapeutic purposes in the form of IVIG as well as several hyperimmune globulins. Current knowledge on the therapeutic use of normal Igs is based on the discoveries made by several pioneers of the field. In this paper, we review the evolution of IVIG over the years. More importantly, the process started as an s.c. replacement in γ globulin-deficient patients, underwent metamorphosis into i.m. Ig, was followed by IVIG, and is now back to s.c. forms. Following successful use of IVIG in immune thrombocytopenic purpura, there has been an explosion in the therapeutic applications of IVIG in diverse autoimmune and inflammatory conditions. In addition to clinically approved pathological conditions, IVIG has been used as an off-label drug in more than 100 different indications. The current worldwide consumption of IVIG is over 100 tons per year. © 2018 by The American Association of Immunologists, Inc.