Diagnosis of periprosthetic joint infection (PJI) remains a real challenge to the orthopedic community. Currently, there is no single standard definition for PJI. This communication presents the diagnostic criteria that have been proposed by a workgroup convened by the Musculoskeletal Infection Society. The diagnostic criteria were developed after the evaluation of available evidence. The role of every diagnostic test was examined, and the literature was reviewed in detail to determine the threshold for each test. It is hoped that the proposed definition for PJI will be adopted universally, bringing standardization into a field that has suffered extensive variability and heterogeneity.