Methicillin-resistant S. aureus has emerged as a nosocomial pathogen of major importance in pediatric patients. Infection occurs most often in hospitalized individuals with underlying predisposing medical conditions. Any body site may be involved, and bacteremia frequently occurs concomitantly. Vancomycin is the antibiotic of choice for serious MRSA infections; PRPs and cephalosporins generally are not effective. The likelihood of an adverse outcome of infection increases with the severity of an underlying condition and delay in institution of appropriate therapy. Infection control measures have met with only limited success in eradicating MRSA from the hospital environment. Methicillin-resistant S. aureus is likely to remain of considerable clinical significance to physicians caring for seriously ill children.