Infection of a primary joint arthroplasty can be a life-changing event for a patient. When the infecting organism demonstrates antibiotic resistance, treatment can be prolonged, and the chances for a successful outcome may be decreased. Antibiotic resistance has been an evolutionary process since the introduction of pharmacologic treatment and until recently has been more problematic with nosocomial types of infections. Methicillin-resistant Staphylococcus aureus skin infections within the community among school or sports teams has been a recent cause for concern. Hospitals have implemented screening and/or isolation procedures to reduce the risk of spreading these resistant organisms and identify patients colonized with resistant organisms. These measures have been successful in patients undergoing total joint arthroplasty. It is important for the orthopaedic surgeon to be knowledgeable about the emergence of resistant bacteria, preoperative and intraoperative screening guidelines, and postoperative considerations to prevent resistant organism infections in total joint arthroplasty patients.