MRSA has become the most common gram-positive bacterial species associated with serious hospital-acquired infections and significant health-care costs. Hospital-acquired pneumonia caused by MRSA are common. Until recently, vancomycin is the primary treatment option for infections caused by MRSA for many years. Association between an increasing of vancomycin use, there is growing concern that vancomycin has diminished activity for MRSA infections. High rates of vancomycin failure in MRSA infections have been increasingly reported over time. Traditionally, a dosing of 1 gram every 12 hours to achieve serum trough concentrations of 15 to 20 mg/L may not be sufficient when empirically or definitely covering MRSA infection with MIC more than 1 mg/L. Based on many study results, an AUC/MIC ratio of 400 has been advocated as a target to achieve clinical effectiveness with vancomycin. Therefore, probability of achieving target AUC/MIC is zero if vancomycin MIC 2 mg/L with low or high-dose vancomycin. Vancomycin has large molecule and high polarity resulting of poor penetration to epithelium lining fluid of lung. Several studies have suggested that vancomycin may not be adequate serum concentration for treatment of pneumonia attributed to MRSA. It also has a variability of pharmacokinetic data. As all mentioned, vancomycin has some limitations and should be taken into consideration. This information will be useful for healthcare personals for considering of vancomycin in order to increase efficacy and decrease treatment failure.