During the last several decades, the use of appropriate antibiotics has significantly improved our ability to prevent and treat infection that occurs after implantation of an orthopedic device. Despite improved prevention and treatment of this condition, patients who develop an infection secondary to implantation of an orthopedic device face increased mortality, morbidity, and/or delayed recovery. The presence of an orthopedic device significantly reduces the number of bacteria required to produce colonization and decreases the ability of the body's own defense mechanism and antibiotics to resolve this condition. Efforts devoted to prevention of infection are much more effective than those spent treating the condition once it has developed. Pretreatment of patients with antibiotics and the use of ultra clean surgical rooms have been shown effective. Prevention will become increasingly important as antibiotic resistant strains of bacteria become more prevalent and the number of arthroplasty procedures performed also increases.