The widespread use and dramatic success of prosthetic joint implant surgery (arthroplasty) has greatly improved the quality of life for many individuals suffering from degenerative, arthritic, or injured joints. However, in a number of cases, recipients experience discomfort at the arthroplasty site that can signal biomechanical failure, or periprosthetic infection of the joint, or both. In fact, infection remains a devastating obstacle, preventing arthroplasty from being an almost perfect medical procedure. Existing tests for the diagnosis of infection in orthopedics are disappointing because of the relatively high frequency of false negative results. To overcome this shortcoming, and to reduce the number of infected revision arthroplasties, a methodology based on molecular biology has been established. The method allows the rapid, sensitive and accurate diagnosis of orthopedic infections, and should aid the clinician with treatment regimens, surgical decisions, and overall patient management in the growing arthroplasty population.