As the number of joint prosthesis replacements worldwide increases exponentially, prosthetic joint infection (PJI), associated with prosthetic implants, has become a devastating complication associated with high morbidity and substantial cost. Patients who develop PJIs typically require extended hospitalization, additional surgical procedures, and long courses of parenteral antimicrobials. Defining the diagnostic criteria is complicated by patient heterogeneity. No single routinely used clinical test has been shown to achieve the ideal sensitivity, specificity, and accuracy for the diagnosis of PJI. Goals of treatment are to eradicate infection, prevent recurrence, and preserve mechanical joint function. Meanwhile, preventive strategies should be used in a timely and appropriate fashion. The present review will discuss the diagnosis, management, and prevention of PJI.