The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in many countries is increasing and, in hospitals in some areas, more than half of all S. aureus disease isolates are MRSA. MRSA strains are becoming increasingly multiresistant, and have recently developed resistance to vancomycin, used successfully to treat MRSA for more than 30 years. This review summarises recent studies that have elucidated the evolutionary history of MRSA. The first MRSA isolate evolved from a sensitive, epidemic strain prevalent in Europe, and its progeny—the first MRSA clone—quickly spread to other continents. Analyses of epidemic MRSA isolates from hospitals in different countries by molecular methods, including multilocus sequence typing (MLST) and DNA microarray analysis, reveal that MRSA strains have evolved separately within five distinct epidemic, sensitive lineages. However, resistance has been transferred to S. aureus on many more than five occasions, as some lineages have acquired different structural types of the element carrying the methicillin resistance gene. The emergence of MRSA as a community pathogen has been noted in several countries, and MLST and SCCmec typing have been used to demonstrate that community-acquired MRSA strains are typically related only distantly to hospital MRSA strains, and thus represent novel acquisitions of SCCmec.