The risk of nosocomial infection in full term neonates cared for in well-baby nurseries can be minimized if personnel adhere to fundamental infection control principles. Neonates who require intensive care face a much greater risk of infection, particularly if they have very low birthweights. Such babies have seriously impaired host defenses, require prolonged hospital stays, and are exposed to a variety of invasive diagnostic and therapeutic procedures. They are extremely vulnerable to a wide range of nosocomial pathogens, including bacteria, fungi, and viruses, many of which are frank opportunists. Although it may not be possible to prevent all, or even most of these infections, careful attention to barrier precautions, adequate staffing, sound NICU design, and prompt case identification and cohorting can reduce the risk substantially.