➤ There is no absolute test for the preoperative diagnosis of periprosthetic joint infection (PJI); thus, clinical practice relies on a combination of supportive tests and criteria.➤ Novel serum and synovial tests have improved our ability to diagnose PJI. The 2018 evidence-based algorithm for PJI diagnosis provides weighted scores for serum markers, as well as synovial markers, to facilitate diagnosis when major criteria such as positive cultures or a sinus tract are not present.➤ Culture-independent technologies such as next-generation sequencing can facilitate pathogen identification, particularly in the setting of culture-negative PJI.➤ Despite recent developments, PJI diagnosis remains challenging and warrants further innovation.