The incidence of vancomycin resistance among enterococci, and Enterococcus faecium in particular, has increased sharply in the last few years. This shift toward infection with resistant Gram-positive organisms is thought to be the consequence of certain features specific to the intensive care setting: a high concentration of severely compromised patients; continued use of indwelling devices and invasive procedures; and widespread, empiric use of antimicrobial agents directed against Gram-negative bacilli. Measures that can be taken to prevent the development of bacterial resistance in the ICU include strict adherence to infection control policies and asepsis, and rational use of antibiotics. Current antimicrobial regimens for serious enterococcal infections consist of a combination of ampicillin, penicillin G, or vancomycin plus streptomycin or gentamicin. High levels of resistances among some enterococcal isolates, however, may render these strategies ineffective. A new agent, quinupristin/dalfopristin (RP 59500), has demonstrated encouraging in vitro activity against vancomycin-resistant E. faecium. Initial clinical reports, though limited, are similarly promising. Although phase III clinical trials with RP 59500 are not completed, the agent is available through an emergency-use program for patients with severe Gram-positive infections who cannot tolerate or do not respond to all other clinically appropriate antibiotics.