Despite control efforts, the incidence of nosocomial infections due to vancomycin-resistant enterococci (VRE) continues to increase in the United States. VRE are thought to spread primarily by cross-contamination. Recent molecular epidemiologic studies have refined our understanding of this phenomenon. If VRE are not controlled soon after introduction into a hospital, sporadic cases may evolve into a monoclonal outbreak, which may then evolve to polyclonal endemicity. An intervention that is effective in containing VRE in one setting may be ineffective in another. Control of VRE where they are endemic is particularly challenging. Although eradication of endemic VRE may not be possible, aggressive, multifaceted programs have been successful in diminishing the problem. A mathematical model of transmission of VRE and the effect of infection control measures in settings where they are endemic has been reported. The use of such a model may allow more precise determination of the impact of control strategies in the future.