Methicillin-resistant Staphylococcus aureus was initially detected in Europe in the 1960s, soon after the introduction of methicillin. Naturally-resistant strains were isolated in some countries before the use of methicillin or related agents. These strains probably spread initially from one or more ancestral genetic clones in natural populations of S. aureus by horizontal transfer and recombination. These original strains, possibly emerging in many countries, then increased in numbers and diversity in hospitals as a result of selection by exposure to antibiotics and by cross-infection. After a decline in the 1970s, new epidemic strains that differed from the original MRSAs emerged in Australia, the United States, and the Irish Republic and have now reached global proportions. Most strains are highly resistant to antibiotics and some are only sensitive to vancomycin or teicoplanin. Intercountry and intercontinental spread has also occurred by transfer of infected or colonized patients or staff. However, the main mode of spread is person-to-person within a unit or hospital and subsequently to other hospitals in the same country. New epidemic strains have continued to emerge and decline for unknown reasons. On the basis of evidence from countries where MRSA is not a problem, it has been suggested that early detection, effective infection control measures, and rational antibiotic use will limit the transmission of these organisms; however, spread is still increasing in many countries.