Diagnosis of periprosthetic joint infection (PJI), one of the major causes of failure of total joint arthroplasty, continues to pose a challenge. One of the major reasons is the lack of a ''gold standard'' to distinguish between septic and aseptic failure. Isolation of an infecting organism in otherwise confirmed PJI also may be challenging as organisms usually reside as a biofilm on the surface of the implant. This limitation can be overcome by using nonculture diagnostic tests, including inflammatory serologies, joint aspiration with fluid cell count analysis, and tissue biopsy. Imaging tests are limited in their ability to differentiate septic from aseptic joints and also are limited by cost. While radionuclide imaging modalities have yielded improved results, low accuracy for diagnosis of PJI remains. In recent years there have been some advances in diagnosis of PJI, including creation of evidence based guidelines, creation of a consensus definition of PJI, and emergence of new diagnostic tests and improved understanding of current tests. This review article will highlight some of these advances.