Systemic infection continues to be an important cause of morbidity and mortality in newborn infants. The incidence is particularly high in very low birthweight neonates who require intensive care treatment. Respiratory diseases, total parenteral nutrition, prolonged intravascular cannulization, broad spectrum antibiotics and H2blocker therapy are factors associated with an increased risk of septicaemia. The very different and distinct pattern of early versus late bacterial infection, and congenital versus postnatally acquired systemic fungal infection, is emphasized. A new syndrome of invasive cutaneous fungal dermatitis is described in the smallest and the most immature babies. Viral infection is increasingly recognized as an important entity, and potential preventive and treatment strategies are highlighted.