Periprosthetic joint infection (PJI) is a severe complication after total knee arthroplasty (TKA), occurring in approximately 0.3% to 3% of all cases. With growing populations and increasing age, this kind of pathology is worldwide growing its social and economic effects. Many risk factors have been identified but a proper and accurate diagnosis and choice of treatment seem to be characterized by an enormous evolution. Diagnostic features such as clinical and radiological elements are loosening their predictive value. New biomarkers and molecular elements seem to be more precise and accurate in confirming PJI. Anyway, lots of them are still under study. About treatments, decisions of surgeons should not be related to their experience or preference, but every choice should have proper indications. Double-stage treatments should be practiced only in few conditions. Cheaper management such as irrigation or single-stage surgery can be considered for several conditions.