Daptomycin is a novel cyclic lipopeptide antibiotic that provides rapid bactericidal activity against gram-positive pathogens in vitro, including methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, vancomycin-resistant S. aureus, penicillin-resistant Streptococcus pneumoniae, and ampicillin- and vancomycin-resistant enterococci. The United States Food and Drug Administration recently approved daptomycin for treatment of complicated skin and skin-structure infections. Its efficacy in the treatment of more-serious infections (e.g., staphylococcal bacteremia) is under investigation. As an intravenous agent that is administered once per day, it offers a convenient regimen for therapy that is continued after discharge, with a side effect profile that appears minimal and manageable. Spontaneous acquisition of resistance in vitro is rare, and hopefully this characteristic will extrapolate into the clinical setting. The rapid bactericidal activity, low potential for resistance, and promising safety profile associated with this agent will make it a useful addition to our growing armamentarium of antibiotics active against gram-positive pathogens.