Staphylococcus aureusis one of the ESKAPE (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies) pathogens among which multidrug resistance has emerged. Resistance to methicillin has resulted in clinicians using the antibiotic of last resort, vancomycin, to treat infections caused by methicillin-resistantS. aureus(MRSA). However, excessive use and misuse of vancomycin are major causes of resistance amongS. aureusstrains. South Asia encompasses ~25% of the world’s population, and countries in South Asia are often characterized as low- and middle-income with poor healthcare infrastructure that may contribute to the emergence of antibiotic resistance. Here, we briefly highlight the mechanism of vancomycin resistance, its emergence inS. aureus, and the molecular epidemiology of non-susceptibleS. aureusto vancomycin in the South Asian region.