Over the last 2 decades, enterococci, formerly viewed as organisms of minimal clinical impact, have emerged as important hospital-acquired pathogens in immunosuppressed patients and intensive care units (ICUs). Vancomycin resistance in enterococci is increasing steadily. Vancomycin-resistant enterococci (VRE) composed 26% of nosocomial enterococci in 1999, a 47% increase from 1994 to 1998. More that 25% of ICU enterococci are resistant to vancomycin. Antimicrobial therapy is problematic for all VRE, but particularly when bactericidal activity is necessary. Quinipristin-dalfopristin and linezolid are 2 new approved antimicrobials for the treatment of recalcitrant infections caused byVRE. Control of the transmission of VRE, although successful in preventing infections, is neither simple nor inexpensive, and VRE has become endemic in many hospitals. However, endemicity poses serious risks to the health of current and future patients, and of itself, is expensive. Data on the cost-effectiveness of VRE prevention programs are currently lacking and urgently needed; however, because the added cost of a single VRE infection far exceeds those of gowns, gloves, and screening, it seems likely that such control programs represent significant cost savings for those hospitals willing to undertake them.