Daptomycin is a cyclic lipopeptide with a rapid bactericidal effect against Gram-positive bacteria. The pharmacokinetic properties of this drug allow once-daily intravenous infusion as the best posology (including a 2-minute bolus). Because of its ease of administration and excellent safety profile, daptomycin is a first-line agent for use as outpatient antimicrobial parenteral therapy (OPAT). The best evidence supporting this indication exists for the treatment of complicated and uncomplicated skin and soft tissue infections, as well as osteoarticular infections caused by Gram-positive bacteria. For the remaining indications, the use of daptomycin as OPAT should be analyzed in each patient. Information from the EUCORE Registry in Spain indicates that daptomycin has high rates of treatment success in both hospitalized patient and in those included in OPAT programs.