The objective of this review was to summarize the current knowledge base on the prevention of nosocomial infections in pediatric intensive care units (PICUs). Healthcare-associated infections (HAIs) are a crucial problem in PICUs because of their impact on patient outcome, length of hospital stay, and costs. Studies published between 1998 and 2011 were identified using the MEDLINE and Cochrane databases. Randomized, cohort, case-control studies, and meta-analyses concerning global strategies of prevention, general organization of the wards, general recommendations on antibiotic management, and measures for the prevention of ventilator-associated pneumonia (VAP), bloodstream infections (BSIs), urinary tract infections (UTIs), and surgical site infections (SSIs) were incorporated. Limits of age from 1 month to 18 years were used. When recommendations could not be supported by the pediatric literature, adult studies were also reviewed. This review excludes the neonate population. Specific pediatric data are often lacking so as to establish specific evidence-based pediatric recommendations. This review underlines the absolute necessity of pediatric studies and to harmonize the definitions of HAIs.