Immunoglobulins are key effector molecules in the humoral immune response. Intravenous polyspecific immunoglobulin (IVIG) is a preparation of polyclonal serum immunoglobulins, typically IgG, from thousands of donors. It has been used as adjunctive therapy in critically ill patients with severe infections, i.e. sepsis, septic shock, and necrotizing soft tissue infections. IVIG has been used for patients with severe invasive group A streptococcal infection since the early nineties and off-label use of IVIG for necrotizing soft tissue infections is common. It is also used for a variety of autoimmune, inflammatory, and immunodeficiency diseases. A meta-analysis of the clinical studies available for IVIG use in group A streptococcal toxic shock syndrome indicates a survival benefit. A blinded, placebo-controlled clinical trial (INSTINCT) assessed the effect of IVIG in 100 intensive care unit patients with necrotizing soft tissue infections, including all bacterial etiologies. The study did not demonstrate any effect on self-reported physical functioning at 6 months. In this chapter, we review the mechanisms of action of IVIG and the clinical studies that are available for necrotizing soft tissue infections as well as severe group A streptococcal infections.