Daptomycin is a bactericidal lipopeptide with a spectrum of activity similar to that of linezolid or quinupristin-dalfopristin. This spectrum includes methicillin-resistant staphylococci and VRE; however, MICs are much lower for the former than the latter. Daptomycin has poor oral bioavailability and thus is only available as a parenteral product. Its long pharmacologic half-life allows for once-daily dosing (approved at 4 mg/kg every 24 hours in skin and soft-tissue infection and 6 mg/kg, every 24 hours in the treatment of bacteremia and right-sided endocarditis); dosage adjustment is necessary in the presence of kidney disease. IDSA recommends 8–10 mg/kg daily to treat serious infection; doses up to 12 mg/kg are recommended by some experts for treatment of vancomycin-resistant Enterococcus. The primary adverse event associated with daptomycin is a reversible, dose-dependent myopathy observed with more than 7 days of therapy. Considering this complication, monitoring of serum creatine kinase levels is recommended, particularly in those patients receiving long-term therapy. Daptomycin cannot be used in the treatment of primary respiratory tract infection because pulmonary surfactant binds daptomycin, resulting in subtherapeutic free drug concentrations in pulmonary secretions.