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Vancomycin-resistant Enterococci (VRE) infections are problematic due to limited availability of anti-VRE agents and their potential for adverse effects and drug interactions. This review focuses on the role of daptomycin in treating VRE infections by summarizing key points of relevant clinical studies. Higher doses of daptomycin (≥ 6 mg/kg), as compared to standard doses, were found to be safe in terms of creatinine phosphokinase elevation and associated with successful infection outcomes and microbiological clearance. High doses are especially important in treatment of infections involving elevated daptomycin minimum inhibitory concentration (MIC) values (3–4 μg/mL). Daptomycin, especially in higher doses, has been shown to be an effective and safe VRE agent for a variety of serious infection types, such as catheter-associated bloodstream and intra-abdominal infections, and for different populations including oncology. Infections involving higher daptomycin MIC values were associated with previous daptomycin use and prosthetic devices.