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Staphylococcus aureus is a foremost human pathogen, which causes an array of infections in the community and the healthcare setting. Although much of the attention is focused on the methicillin-resistant S. aureus (MRSA), the methicillin-susceptible counterpart (MSSA) remains a prime species in infections. The molecular epidemiology of S. aureus, particularly of MRSA, demonstrated a rapid evolution in the past few years. Worldwide surveillance has suggested that MRSA is a serious problem in all continents, which underpin the dire need to map the global epidemiology of S. aureus, utilizing currently available advanced tools.S. aureus can effortlessly come over the use of antibiotics and acquire resistance. The MRSA epidemiology has been budding since its initial outbreak, which underpins a comprehensive medical approach to curb this pathogen. Vancomycin has been considered to be the drug of choice for years but the emergence of resistance has challenged its utility. Approximately, in the last one decade, a limited number of anti-MRSA antibiotics have been approved for treatment. Recent investigations highlight the prevalence of a genetically diverse clonal population of MRSA, which suggest potential tools to trace out the origin of the latter.