Multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are endemic in healthcare settings in the United States and many other countries of the world. Nosocomial transmission of MRSA serves as a source of hospital outbreaks, and recent reports of vancomycin-resistant S aureus strains in the United States emphasize the need for better control of MRSA and other resistant bacteria within healthcare settings. Colonization with S aureus or MRSA is relatively common in both healthy and hospitalized individuals, most often involves the anterior nares, and is frequently asymptomatic. Colonization increases risk of infection. Patient-to-patient transmission of MRSA within healthcare settings primarily occurs via carriage on the hands of healthcare workers. The Society for Healthcare Epidemiology of America (SHEA) has developed guidelines for the prevention of transmission of MRSA and vancomycin-resistant enterococci within healthcare settings, and chief among the recommendations is an emphasis on adherence to hand hygiene guidelines. Other measures that may prevent the nosocomial transmission of MRSA include improved antibiotic stewardship, staff cohorting, maintenance of appropriate staffing ratios, reductions in length of hospital stays, contact isolation, active microbiologic surveillance, and better staff education. Currently, the efficacy of many of these individual infection control interventions remain in doubt. Many studies reporting improvement in infection control outcomes (eg, reduced transmission, decreasing prevalence) involve simultaneous institution of several of these measures, making it impossible to tease out the effects of any of the individual components. Nonetheless, the best approach in the current environment probably involves hand hygiene plus a careful assessment of an institution’s particular circumstances, applying more aggressive procedures such as patient isolation, staff cohorting, and active surveillance cultures, as indicated.