Nosocomial infections are responsible for significant morbidity and late mortality among neonatal intensive care unit patients. The number of neonatal patients at risk for acquiring nosocomial infections is increasing because of the improved survival of very low birthweight infants and their need for invasive monitoring and supportive care. Effective strategies to prevent nosocomial infection must include continuous monitoring and surveillance of infection rates and distribution of pathogens; strategic nursery design and staffing; emphasis on handwashing compliance; minimizing central venous catheter use and contamination, and prudent use of antimicrobial agents. Educational programs and feedback to nursery personnel improve compliance with infection control programs.