Vancomycin is a glycopeptide bactericidal agent mainly used to treat serious infections caused by Gram-positive bacteria such as drug-resistant Staphylococcus aureus and Enterococcus. In critically ill patients, the incidence of infection is high due to the destruction of physiological barriers, and drug-resistant bacteria infections are common. In critically ill patients the pharmacokinetics of vancomycin is greatly altered by capillary leakage and organs dysfunction, so it is wise to use it individually in different critical situations. Literatures on the proper and rational use of vancomycin in critically ill patients is reviewed to provide ideas for optimizing the administration of this agent in these special populations.