The Author starts from the considerations developed by various scientific associations, such as EBJIS, MSIS, and WAIOT, and by the Consensus Conference in Philadelphia in 2018, on the definition of periprosthetic joint infection (PJI) and how to arrive at the diagnosis of this pathology regarding the values found in various tests. It must be considered that the diagnostic evaluation involves the set of various aspects evaluated starting from the anamnesis, then the clinic, the various tests both on the blood (ESR, PCR, fibrinogen, Interleukin 6, D-dimer) and on the synovial fluid, with all the possible increases data from different pathologies and different patient conditions which can alter the outcome. The search for the pathogenic germ that allows the use, on the basis of the antibiogram, of targeted antibiotics. The values can be entered into a score which, added together, can guide us in the diagnosis of PJI. The latest tests used for identifying the germ are also taken into consideration, especially in low infections, such as the molecular test that uses the genome of the bacterium. Associated with these tests, there are instrumental ones such as nonspecific radiography for the type of pathogen. Fistulography, which allows us to highlight the starting area of a septic focus or a collection, with the ultrasound, to be able to aspirate it. MRI, CT, and PET-CT, and, finally, scintigraphy with autologous marked leukocytes and the Spect-Tc, the golden standard of septic diagnostics, even if operator dependent. Always, in diagnostics, the use of detection systems on explanted prostheses and on tissues, such as sonication, is taken into consideration, and the use of Dithiothreitol (DTT).