Antimicrobial resistance among Gram-positive organisms continues to increase and has reached epidemic proportions in a number of countries and within medical centers worldwide. Daptomycin is a new lipopeptide antibiotic with rapid bactericidal activity against Staphylococcus aureus. It is also active against coagulase-negative staphylococci, enterococci and streptococci. It exerts its effect through cell membrane disruption that results in dissipation of the membrane potential. Daptomycin exhibits a prolonged postantibiotic effect and is well tolerated. In Phase III clinical trials, daptomycin was found to be similar in efficacy to standard therapy in complicated skin and skin structure infections. More recently, it was approved for the treatment of S. aureus bacteremia and right-sided endocarditis. Daptomycin is not indicated for pulmonary infections. Preliminary data suggest that daptomycin may be effective in urinary tract, bone and joint infections. However, randomized clinical trials are needed to confirm these findings. Daptomycin is an effective antimicrobial agent for the treatment of various serious Gram-positive infections, especially those caused by methicillin-resistant S. aureus.