Daptomycin is a lipopeptide antibacterial with rapid in vitro activity against Gram-positive cocci. It is approved for use in patients with complicated skin and skin structure infections (cSSSIs) caused by specified Gram-positive cocci. In vitro, daptomycin was active against Staphylococcus aureus (including meticillin-resistant strains), Streptococcus pyogenes, S. agalactiae, group C and G beta-haemolytic streptococci and vancomycin-susceptible Enterococcus faecalis. Bactericidal activity in vitro was rapid and concentration dependent. In two randomised, investigator-blinded, multicentre trials in patients with cSSSIs, intravenous daptomycin 4 mg/kg once daily was as effective as standard therapy (intravenous semi-synthetic penicillin 4-12 g/day or vancomycin 1 g 12-hourly). Clinical success rates assessed 6-20 days after treatment end were 82.1% in daptomycin recipients and 82.9% in recipients of standard therapy (pooled data). In patients with cSSSIs, the adverse event profiles of daptomycin and vancomycin were similar. Creatine phosphokinase (CPK) levels increased in 2.8% of daptomycin recipients and 1.8% of patients who received standard therapy; only one daptomycin recipient (0.2%) experienced increased CPK levels and muscle symptoms that were not associated with any comorbid factors.