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Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterocci (VRE) are the two most common healthcare-associated multidrug-resistant organisms. The purpose of this article is to review recent data regarding the epidemiology, control and treatment of these organisms as well as to discuss the emergence of additional antimicrobial resistance determinants.Although the prevalence of methicillin resistance continues to increase among healthcare-associated S. aureus isolates, the incidence of invasive MRSA infections appears to be decreasing. Reduced susceptibility to vancomycin among MRSA isolates has been associated with glycopeptide treatment failure. Resistance to newer antimicrobial agents, such as daptomycin and linezolid, has been described among isolates of MRSA and VRE, further complicating treatment of infections caused by these organisms. Recent studies that have attempted to assess the efficacy of a variety of strategies for the prevention of MRSA and/or VRE transmission and infection, including active surveillance testing, have been published and additional studies are currently underway.MRSA and VRE remain important causes of morbidity and mortality among patients receiving healthcare. The emergence of resistance to additional antimicrobial agents highlights the importance of effective prevention programs. Further study to determine the optimal approaches to treatment and prevention is needed.