The two main indications for the use of intravenous gammaglobulin--antibody replacement therapy and immunomodulation--are pertinent only for a few scenarios in HIV-1 infection. The role of gammaglobulin in the treatment of HIV-1 infection has changed significantly with the introduction of highly active antiretroviral therapy. Antiretroviral drugs have not only controlled the progression of disease but also had far-reaching effects on HIV-1-induced immunologic aberrations. Complete or partial immunologic reconstitution and prevention of immunologic damage have been the hallmarks of success for highly active antiretroviral therapy. This article addresses the use of gammaglobulin before and after the era of effective antiretroviral therapies.