Gram-negative bacilli are the main resistant bacteria that threaten the safety of patients globally, but the treatment failure caused by gram-positive cocci infection also remains a clinical problem. With the insensitivity of resistant gram-positive cocci to glycopeptides and the increasingly upward drift in the minimum inhibitory concentration, the number of cases that are sensitive in vitro but fail in clinical treatment is increasing, there is an urgent need for effective and new antimicrobial agents to treat patients with gram-positive cocci infection. Daptomycin is a new cyclic lipopeptide antibiotic, which has a new antibacterial target, rapid bactericidal activity, and can penetrate the biofilm. It does not lead to the dissolution of bacteria, thus avoid the serious inflammatory reaction due to the release of inflammatory mediators in bacterial content, it has a good clinical application value in the treatment of bacteremia, infective endocarditis, as well as complicated skin and soft tissue infection. In order to treat patients effectively and rationally with daptomycin, professional committee of evidence-based and transformation of infectious diseases of Chinese Research Hospital Association organized domestic experts to write expert opinion on clinical application of daptomycin, so as to provide reference for clinical medical staff.