Abstract: Ceftobiprole is the first fifth-generation cephalosporin in China, which exerts antibacterial activity by inhibiting penicillin-binding proteins (PBPs). It is the first effective β-lactam antibiotic against methicillin-, vancomycin-, linezolid- and daptomycin-resistant Staphylococcus strains including Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative Staphylococcus strains. Ceftobiprole is domestically approved for the treatment of hospital- and community-acquired pneumonia (HAP and CAP), excluding ventilator-associated pneumonia (VAP). Phase 3 global clinical trials of ceftobiprole on the efficacy and safety of acute bacterial skin and skin stucture infections (ABSSSIs) and complicated S. aureus bacteremia (SAB) had been completed and approved by the Food and Drug Administration on April 3 this year. We reviewed advancements in the antibacterial mechanism of ceftobiprole against S. aureus, in vitro antimicrobial activity, domestic and international status of clinical applications and real-world medicine experience. The efficacy and safety of ceftobiprole on S. aureus are discussed in detail to provide reference for clinical treatment.