In the specialty of orthopaedics, methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to infections of the soft tissues, surgical sites, and joints, in addition to increasing disability, mortality, and healthcare costs. Inappropriate prescribing and misuse of antibiotics have led to bacterial resistance and the rapid emergence of MRSA. It is imperative for healthcare providers and facilities to improve quality, promote safety, and decrease costs related to MRSA infections. The healthcare profession and society as a whole play an important role in minimizing the transmission of pathogens, reducing the incidence of MRSA infections, and decreasing the development of future antibiotic resistant pathogens. This article discusses the epidemiology of MRSA and describes evidence-based guidelines pertaining to the prevention, minimization, and treatment of MRSA-related infections. Specific application to orthopaedics are discussed in the context of patient risk factors, perioperative and postoperative prophylaxis, and current trends regarding education and reporting strategies.