An understanding of the prevalence of resistant Staphylococcus aureus and the risk factors for infection with resistant isolates is essential to help clinicians choose appropriate antibiotic therapy. Selection pressure due to prior and inappropriate antibiotic use of any kind seems to be the main driving force behind the increasing rates of multidrug resistance in methicillin-resistant S. aureus (MRSA) strains. Resistance to glycopeptide antibiotics in MRSA has also emerged in recent years, along with increased use of vancomycin to treat serious infections due to MRSA. Infections due to MRSA are associated with significantly increased morbidity, mortality, length of hospital stay, and costs, compared with infections due to methicillin-susceptible S. aureus, despite adjustment for disease severity and initially appropriate antibiotic treatment. Improvements in the preparation and dissemination of antibiograms, along with adequate public reporting of MRSA trends, are needed to address the challenge of choosing appropriate initial antibiotic treatment for MRSA infections.