PURPOSE OF REVIEW: Systemic infections in premature and term infants cause significant morbidity and mortality in spite of appropriate antimicrobial therapy. Consequently, immunotherapy has emerged as a potential adjuvant therapeutic modality to reduce the incidence and mortality associated with neonatal sepsis. RECENT FINDINGS: The most recent findings during the review period include systematic reviews of previously published trials evaluating the use of intravenous immunoglobulin and colony-stimulating factors in neonatal sepsis. In addition, the most recent trials describing the use of antistaphylococcal antibodies, probiotics, glutamine supplementation, recombinant human protein C, and lactoferrin in the prevention and treatment of neonatal sepsis have been reviewed. SUMMARY: Immunotherapy used as an adjuvant for the prevention and treatment of neonatal sepsis holds promise. Clinical trials specifically designed toward the neonatal population and appropriately powered to detect treatment differences are necessary prior to universal recommendation of these therapies in the nursery.