Historically, staphylococci, pseudomonads, and Escherichia coli have been the nosocomial infection troika; nosocomial pneumonia, surgical wound infections, and vascular access-related bacteremia have caused the most illness and death in hospitalized patients; and intensive care units have been the epicenters of antibiotic resistance. Acquired antimicrobial resistance is the major problem, and vancomycin-resistant Staphylococcus aureus is the pathogen of greatest concern. The shift to outpatient care is leaving the most vulnerable patients in hospitals. Aging of our population and increasingly aggressive medical and surgical interventions, including implanted foreign bodies, organ transplantations, and xenotransplantation, create a cohort of particularly susceptible persons. Renovation of aging hospitals increases risk of airborne fungal and other infections. To prevent and control these emerging nosocomial infections, we need to increase national surveillance, "risk adjust" infection rates so that interhospital comparisons are valid, develop more noninvasive infection-resistant devices, and work with health-care workers on better implementation of existing control measures such as hand washing.