The treatment of sepsis with i.v. immunoglobulins (IVIG) is currently regarded as not indicated. Several clinical studies, placebo controlled since 1985, to determine efficacy have failed to prevent fatal outcome, even when IVIG was given at high doses. The prevailing action mechanism put forward by most researchers is the capacity of specific antibodies contained in IVIG to bind to the infectious organism followed by opsonophagocytosis. Recently, IVIG preparations have been shown, both in vitro and in vivo, to profoundly affect the homeostasis of the cytokine network, probably in a way which directs this network from disturbed to regulated functioning. Excessive production and insufficient removal of cytokines due to multiorgan failure of sepsis patients are now known to play a decisive role in progression of sepsis to septic shock. There are researchers wondering whether the newly discovered influence of IVIG on cytokines might not be exploited for the design of improved study protocols, including better selection of the dosage, dosage schedule, association to other treatments and selection of patients. On the side of the IVIG preparations, improvements discussed include spiking of polyclonal preparations with monoclonal antibodies, selection of appropriate production lots and study of the efficacy not only of IgG but also of IgM isotype containing preparations.