There has been a nationwide increase in the incidence of vancomycin-resistant Enterococcus (VRE) reported over the last decade and a half. The heightened concern caused by VRE and the possibility of vancomycin resistance gene transfer to other gram positive organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), led the Centers for Disease Control and Prevention (CDC) and the Hospital Infection Control Practices Advisory Committee (HICPAC) to publish recommendations for the prevention and control of vancomycin resistance. However, in 2002, the first documented case of vancomycin-resistant S aureus (VRSA) was reported in Michigan in an immunocompromised patient with a history of diabetes, peripheral vascular disease, and renal failure. Since then, 2 other cases have been reported: 1 in Pennsylvania in October 2002 and 1 in New York in March 2004. The limited availability of effective antimicrobial agents against vancomycin-resistant strains of Enterococcus and Staphylococcus species and the morbidity, mortality, and cost associated with resistance represent serious reasons for concern. This article presents a general overview of the current literature on the prevention and control of vancomycin resistance and a review of potential antimicrobial agents used in the treatment of VRE, vancomycin intermediate S aureus (VISA), and VRSA infections.