Prosthetic joint replacement is being performed more frequently for patients with prior septic arthritis due to Mycobacterium tuberculosis. Prosthetic joint infection due to Mycobacterium tuberculosis does occur, but is rare. We report the clinical characteristics and outcome of seven cases of Mycobacterium tuberculosis prosthetic joint infection seen at our institution over a 22-year period and summarize the English-language literature regarding current prophylaxis and treatment strategies. Tuberculous prosthetic joint infection most often represents reactivation of prior tuberculous septic arthritis. The diagnosis of tuberculous prosthetic joint disease is often delayed, because a history of prior Mycobacterium tuberculosis septic arthritis is not known. Treatment of tuberculous prosthetic joint infection requires a combined medical and surgical approach. Removal of the prosthesis has been the traditional surgical modality, followed by appropriate antituberculous therapy, but other surgical methods have been used successfully in selected cases. To decrease the risk of reactivation of infection after prosthesis implantation in patients with quiescent tuberculous septic arthritis who have not received prior antituberculous therapy, consideration should be given to preoperative or perioperative antituberculous prophylaxis.