There has been a steady rise in the prevalence of resistant Gram-positive pathogens and concerns about the clinical effectiveness of glycopeptides in treating infections due to Staphylococcus aureus. Daptomycin is a novel lipopeptide antimicrobial agent with activity against Gram-positive organisms, including multi-resistant strains. It is licensed in the USA and Europe for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms at a dose of 4mg/kg once daily. It has also been licensed in the USA for the treatment of S. aureus bacteraemia and right-sided endocarditis at 6mg/kg once daily. It is a safe and well-tolerated antibiotic, particularly at the current dosing regimen. Antimicrobial resistance, whilst being increasingly reported, still remains relatively rare. Further studies are required to determine the role of daptomycin for the treatment of osteomyelitis and septic arthritis, as well as its use in combination therapy.