**1. Introduction**

*Staphylococcus aureus* is a Gram-positive, catalase and coagulase positive strain of bacteria belongs to Micrococcaceae family. Staphylococcus spp. to which these bacteria belong is commonly found in nature and human flora. *Staphylococcus aureus* is generally isolated from community as well as hospital gained infections and have capability to cause superficial to life threatening infections [1–3]. However, the worst scenario in field of microbiology was observed in late 90's when resistance among several microbes including *Staphylococcus aureus* was reported for various antibiotics. *Staphylococcus aureus* was the most prominent threat among all other pathogens due to the rapid emergence of resistance in it. The inappropriate use of antimicrobials in clinical therapy and agriculture, extensive antimicrobial consumption and transfer of antimicrobial resistant genes due to increased anthropogenic activity are potential risk factors for development of antimicrobial resistance and considered as primary reasons responsible for the rapidly growing resistance

in *Staphylococcus aureus* [4–6]. Moreover, the intrinsic virulence of *Staphylococcus aureus*, its nature to adapt to the corresponding environment are some other factors which makes it the foremost challenge for microbiology scientists. Even though, many potential therapeutics have been synthesized/approved by USFDA for the treatment of *Staphylococcus* infections but unfortunately besides this the mortality rate of *Staphylococcu*s bacteraemia is 20-40% [7–9]. Furthermore, the clinical sample (blood samples) of patients with nosocomial infections/staphylococcus infections were investigated which confirmed the resistant strains of *Staphylococcus aureus* against various antibiotics that include first- and second-generation fluroquinolones, β-Lactam antibiotics, trimethoprim sulphamethoxazole and vancomycin etc. [7, 10, 11]. Surprisingly, the number of antibiotics emerging for treatment of this bacteria is directly proportionate to the rapidly evolving resistance mechanisms within *Staphylococcus aureus* to combat the therapeutic efficacy of these antibiotics. In year of 2002-2003 *Staphylococcus aureus* was found resistant to the highly efficient antibiotic vancomycin which left the physicians with no competent antibiotic for its treatment. Subsequently it urged the need to explore more drug targets and novel approaches for new antibiotics to treat staphylococcus infections. Conclusively, the rapid structural and genetic modifications of *Staphylococcus aureus* counterbalance the effect of even magnificent antibiotics. Therefore, various molecular mechanisms of *Staphylococcus aureus* have been deeply explored in the recent past to overcome the life-threatening implications of this resistant bacteria [12, 13]. This chapter enlightens the historical evolution of resistance in *Staphylococcus aureus*, molecular mechanism of resistance for various antibiotics and the modified approaches for its treatment.
