Infection is the second most common cause of prosthetic joint failure. Signs and symptoms associated with prosthetic joint infection may develop weeks or even years following arthroplasty. While some patients with prosthetic joint infection present with findings consistent with acute septic arthritis, many present with pain alone. Morbidity and cost associated with repeat surgery, prolonged medical treatment and joint immobilization render importance to the accurate and timely diagnosis, and appropriate treatment of prosthetic joint infection. No consensus exists, however, in terms of the most cost-effective diagnostic methods or the ideal medical and/or surgical interventions. This review describes diagnostic tests and available treatment for prosthetic joint infection and gives a practical approach to this challenging clinical entity.