Vancomycin is currently the standard treatment of gram-positive bacteria inducted nosocomial infections. However its bactericidal activity may be affected by different factors related to its antibacterial activity, pharmacokinetic properties or the infecting bacteria. Based on these facts, this article reviews the clinical importance that bactericidal activity has against susceptible bacteria and the compromise of this activity due to inadequate pharmacodynamic parameter values. From the bacterial target perspective, the clinical importance of the compromised bactericidal activity due to the decreased susceptibility, tolerance, heteroresistance and resistance is reviewed. In addition the characteristics of an antimicrobial targeted for gram positive nosocomial infections as well as the degree of adhesion to them of the bactericidal antibiotic daptomycin are described.