Per-operative contamination is the most frequent cause of prosthetic joint infection. In other cases, contamination results from bacteremia which may be symptom-free, and this situation defines secondary infection. Several factors, whether isolated or combined, are important to establish this diagnosis: prolonged symptom-free interval, bacterial agent not usually encountered in per-operative infections, presence of a distant septic focus, positive blood cultures, identical bacteria isolated from the prosthesis and the distant focus or blood cultures. A probability score is being devised in order to attribute a value to each of these parameters. Infection may be acute or chronic with prosthetic malfunction, but an acute transitory episode (dental, ENT, cardiovascular or digestive, etc.) may be elicited through questioning the patient. Microbiological diagnosis is mandatory (joint puncture and deep surgical samples, blood cultures, samples from portal of entry) before initiating antibiotic treatment: this treatment will initially be probabilistic, and secondarily adapted. From the surgical point of view, lavage and synovectomy must be conducted after wide incision, with removal of all suspect tissue. Conservation of foreign material must be tested, although its advantage has not been confirmed. After a lapse of 21 days, prosthetic material should be removed, bone interface should be scrubbed and immediate or delayed material replacement should be conducted. Investigation and treatment of portal of entry should be initiated without delay. Prevention of secondary infection consists mainly in investigating and treating all focal infections. Any invasive procedure, whether consisting or not in implantation of foreign material, may be incriminated: venous, bladder catheterization, wounds, dental care, cancer, endoscopy, urinary tract infection. The benefits versus risks derived from antibiotic prophylaxis have not been documented.