Newborn infants, especially premature ones, are uniquely susceptible to a variety of bacterial, fungal, protozoan, and viral infections. The neonate’s host defenses against bacterial, fungal, viral, and parasitic infection are compromised by antibody deficiency, decreased concentration and function of the classic and alternative-complement pathways, defective chemo-tactic and bactericidal activity of polymorphonuclear and mononuclear leukocytes, decreased NK-cell, activity and inadequate production of certain cytokines. Abnormalities are present in the cytotoxic activity of neonatal lymphocytes for virus-infected cells, which likely contributes significantly to severe herpesvirus and cytomegalovirus infections in this age group. The human neonate is uniquely susceptible to overwhelming bacterial, viral, protozoan, and fungal infection. One of the most consistent defects in the host-defense system of the human neonate is in polymorphonuclear leukocyte Chemotaxis toward the site of a microbial invasion. Both placental macrophages and cultured peripheral-blood monocytes from neonates are activated by interferon-gamma to kill the pathogens.