Periprosthetic joint infections are one of the significant complications of arthroplasty and associated with serious patient morbidity. Accurate diagnosis and precise isolation of the pathogenic microorganism is the critical corner stone of efficient treatment. In this review, peroperative diagnostic methods which serve the physician in the pathway of diagnosis are assessed in detail. In addition to peripheral blood tests, a variety of serological, histopathological and molecular methods of synovial fluid and joint tissue gives valuable information to evaluate the differential diag-nosis of infection. In the differential diagnosis of painful prosthetic joint history, physical examination, CRP and sedimentation tests are initial steps. The second and important step is aspiration of synovial fluid from infected joint. If there is still an undiagnosed clinical suspicion, joint aspiration should be repeated or tissue biopsy should be performed. Recognizing the purulent fluid while doing surgery was previously one of the major markers of infection, but this opinion has changed nowadays because of the purulent fluid appearance seen in some revisions of metal-onmetal articulations. It has been understood that the serum leukocyte level and gram staining methods are weak signs of infection while a sinus tract connected with prosthesis is a major indicators.