Periprosthetic infections are rare, but there is evidence to suggest that their frequency may be underestimated. No single laboratory test has perfect sensitivity and specificity for diagnosing infection. Most tests have better specificity when they are performed for patients in whom infection is suspected clinically rather than when they are used as screening tests. Screening test results that may suggest the possibility of infection include elevation of the erythrocyte sedimentation rate and/or serum C-reactive protein level more than three months after an arthroplasty. Most serologic tests are difficult to interpret when the patient has an underlying inflammatory arthropathy. Cultures of aspirated joint fluid can be especially helpful for patients who have symptoms suggestive of infection, but their results are best interpreted two weeks after administration of antibiotics has been discontinued. Joint fluid cell counts may also be helpful, but Gram stains of joint fluid have poor sensitivity and specificity. Criteria for diagnosing infection on the basis of frozen sections of implant membranes have not yet been standardized, but in many laboratories more than five neutrophils per high-power field in five or more fields (excluding surface fibrin) has been found to be suggestive of infection. Most polymerase chain reactions that detect the universal 16S rRNA bacterial gene have problems with false-positive results, but combining a universal polymerase chain reaction with subsequent bacterial sequencing can help improve specificity. Polymerase chain reactions can detect necrotic bacteria, so the clinical importance of positive results of this analysis in the absence of other features of infection remains to be determined.