A rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) has been reported from U.S. hospitals in the last 5 years. This increase poses several problems, including: a) the lack of available antimicrobials for therapy of infections due to VRE, since most VRE are also resistant to multiple other drugs, e.g., aminoglycosides and ampicillin, previously used for the treatment of infections due to these organisms, and b) the possibility that the vancomycin resistance genes present in VRE may be transferred to other gram-positive microorganisms such as Staphylococcus aureus. An increased risk of VRE infection and colonization has been associated with previous vancomycin and/or multiantimicrobial therapy, severe underlying disease or immunosuppression, and intra-abdominal surgery. Because enterococci can be found in the normal gastrointestinal or female genital tract, most enterococcal infections have been attributed to endogenous sources within the individual patient. However, recent reports of outbreaks and endemic infections due to enterococci, including VRE, have shown that patient-to-patient transmission of the microorganisms can occur either via direct contact or indirectly via hands of personnel or contaminated patient-care equipment or environmental surfaces. Prevention and control of the spread of vancomycin resistance will require coordinated, concerted effort from various departments of the hospital, and can only be achieved if each of the following elements is addressed: 1) prudent vancomycin use by clinicians, 2) education of hospital staff regarding the problem of vancomycin resistance, 3) early detection and prompt reporting of vancomycin resistance in enterococci and other gram-positive microorganisms by the hospital microbiology laboratory, and 4) immediate implementation of appropriate infection-control measures to prevent person-to-person transmission of VRE.