Methicillin-Resistant Staphylococcus aureus (MRSA), manifested as a primary cause of skin infections, was invasive among healthy adults and children with clinical, epidemiologic, and bacteriologic characteristics distinct from healthcare-associated MRSA (HA-MRSA) resulting in increased length of hospitalization, healthcare costs and increased mortality. Nonetheless, vancomycin 1 was considered as the standard therapy. However, the limitations of vancomycin 1 application in clinical practice were represented by a progressive increase in Methicillin Resistant S. aureus (MRSA) Minimum Inhibitory Concentrations (MIC), drug-related toxicity, and the lack of an oral formulation. Vancomycin 1 might be inferior to beta-lactams for bacteremia treatment because of Methicillin Susceptible Staphylococcus aureus (MSSA) in children. Vancomycin 1, a glycopeptide antibiotic, was first isolated in 1953 as a natural occurring antimicrobial agent produced by soil bacterium Amycolatopsis orientalis. Vancomycin 1 was approved for use in 1958 as a common antibiotic in treating rapidly growing penicillin-resistant Staphylococcus species. However, this antibiotic was not a primary choice of the treatment owing to its poor oral bioavailability and its various adverse effects. The evolution of Pseudomembranous enterocolitis, coupled with the spread of Methicillin Resistant Staphylococcus aureus (MRSA), led to the re-emergence of positive bacteria that were resistant to less-toxic agents. In addition, vancomycin 1 was used in patients who were intolerant or allergic to beta-lactams. This review encapsulates the strategies for the clinical management of MRSA.