Health care-associated infections in the NICU result in increased morbidity and mortality, prolonged lengths of stay, and increased medical costs. Neonates are at high risk of acquiring health care-associated infections because of impaired host-defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of their skin, use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotic agents. This clinical report reviews management and prevention of health care-associated infections in newborn infants.