While the overall incidence of infection has remained constant at approximately 7/1000 livebirths, the last decade has witnessed a reduction in early onset infections and a relative increase in nosocomial sepsis, chiefly with coagulase-negative staphylococci. Immaturity of host defence mechanisms contributes to an increasing susceptibility to infection with decreasing gestational age and birth weight. In the past, efforts to enhance host defence have included the use of granulocyte infusions, fresh frozen plasma, exchange blood transfusions and immunoglobulin therapy. Current trials are investigating the use of agents which enhance endogenous defence mechanisms, such as, recombinant human granulocyte colony-stimulating factant and recombinant human granulocyte-macrophage colony-stimulating factor and of pentoxifylline. In the meantime strict attention to handwashing and aseptic technique remain the best methods of preventing nosocomial sepsis.