Infections with methicillin-resistant Staphylococcus aureus (MRSA) are an ever growing problem in the community, hospitals, and for orthopedic surgeons in particular. A conscious effort must be made to deal with this pathogen prior to total joint arthroplasty procedures. The drastic increase in prevalence of surgical-site infections (SSIs) after total joint replacement surgery has proved to be a major health care burden for both patients and surgeons from both a medical and financial standpoint. The development of screening techniques for detection of MRSA colonization in patients being admitted to hospitals is steadily increasing popularity. Particularly nasal swab rapid polymerase chain reaction detection of MRSA allows surgeons to identify patients at high risk for postoperative SSI. A variety of treatment regimens for eradication of MRSA colonization from the nares of surgical patients have surfaced, such as topical mupirocin prior to undergoing surgery. Decolonization of MRSA in patients undergoing joint arthroplasty procedures has demonstrated encouraging initial results in preventing SSIs and should be a serious focus of the future for orthopedic surgeons.