The use of intravenous immunoglobulin (IVIG) for the prevention and treatment of sepsis in neonates is appealing because of the relative immunodeficiency of the neonate and the desire to improve the relatively poor outcome even with optimal antimicrobial treatment. The effectiveness of IVIG for these uses has been studied in numerous prospective as well as retrospective small and large trials that have had discordant conclusions. Meta-analysis demonstrates the marginal but significant benefit of prophylactic IVIG administered shortly after birth in preventing early onset sepsis in premature low birth weight newborns (P = .0193, two-sided). The expense of prophylactic use of IVIG administration for the relatively large premature newborn population given the minimal benefit as demonstrated by original studies and by meta-analysis is not justified. In contrast, meta-analysis of studies of IVIG for the treatment of neonates with sepsis shows a significant and unequivocal sixfold decrease in the mortality rate (P = .007, two-sided) when IVIG is administered in addition to standard therapies. The additional benefit of decreasing the risk for acute mortality indicates that the inclusion of IVIG should be considered a part of the routine therapy of neonatal sepsis.