Recent interest in the study of Staphylococcus aureus derives from the high frequency of antibiotic-resistant strains that cause frequent outbreaks of infection, especially methicillin-resistant S. aureus (MRSA). The objective of this chapter was to study the population genetic structure and the origin of MRSA isolation. Classification of staphylococcal cassette chromosome mec (SCCmec) is the most important method to identify and define the S. aureus methicillin-resistant clonal nature. Molecular epidemiological studies have demonstrated dissemination patterns of few strains which are responsible for the important worldwide problem. There is a predominance of pandemic clones of MRSA associated to hospital-acquired infections (HA-MRSA) which has been replaced today by community-acquired strains (CA-MRSA). Understanding the epidemiology and clonality of S. aureus infections has important implications for future efforts to control of the emergence of multidrug-resistant strains and the spread of clones resistant and sensible to methicillin.