Daptomycin is a novel bactericidal antibiotic with excellent activity against gram-positive organisms. It is a large cyclic lipopeptide with a unique mechanism of action. Daptomycin is given once a day and is renally cleared, requiring dose adjustment in patients with impaired renal function. Unfortunately, there have been case reports of resistant gram-positive organisms. Daptomycin is generally well tolerated, though myopathy has been reported. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors should be stopped in patients on daptomycin. Daptomycin shows promise in experimental models of endocarditis, meningitis, ventriculitis, and peritonitis, and is currently approved for use in skin and soft-tissue infections. Daptomycin is a welcome newcomer to the gram-positive antimicrobial arsenal.