Infection control has a particularly important role in paediatric hospitals and must take into account the specificity of the needs and environment of the paediatric patient. Children are susceptible to infections that are prevented in older patients by vaccination or previous natural exposure. Consequently, the nosocomial pathogens and most common health-care-associated infection sites in children differ from those observed among adults. The immunological naivety of young children, especially neonates, translates into an enhanced susceptibility to many infections with important health consequences as well as higher rates and longer duration of microorganism shedding. In particular, respiratory virus infections, rotavirus, varicella zoster virus, and pertussis represent persistent challenges in children's hospitals. Specific factors such as the use of breastmilk, toys, or therapy animals are associated with an increased risk for health-care-associated infections. We review the emergence of antimicrobial-resistant organisms and strategies to prevent health-care-associated infections in the paediatric setting.