Daptomycin is a lipopeptide antibiotic that exhibits bactericidal activity against a range of Gram-positive bacterial pathogens including strains resistant to other antibiotics, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Daptomycin is licensed both in the USA and Europe for the treatment of complicated skin and skin-structure infections and in the USA this has recently been expanded to include bacteremia and right-sided endocarditis due to Staphylococcus aureus. A marketing authorization application for this indication is currently under consideration by the European Medicines Agency. The pharmacokinetic and pharmacodynamic properties of daptomycin allow for once-daily dosing, although it is recommended that the dosing interval be increased to 2 days in patients with renal impairment. Clinical data generally indicate that daptomycin is well tolerated, but nonetheless concerns persist regarding potential muscle toxicity. Emergence of resistance to daptomycin has been reported, highlighting the need for prospective surveillance to determine the extent of this potential problem.