Prosthetic joint implantations improve patients' quality of life but are associated with complications, including aseptic failure and prosthetic joint infection (PJI). Biofilms are the essential factor in the persistence of infection. Early postoperative and acute hematogenous infections are usually easily diagnosed; however, late chronic infections are challenging to predict. Joint aspiration with differential cell counts appears to be a very useful test. New microbiological techniques (i.e., implant sonication and molecular studies) are promising tools. Main objectives of treatment are to alleviate pain, to restore the function and to eradicate the infection. In deciding the best approach for an individual patient, several factors should be considered: the type of the infection, presence of loosening, functional prognosis, etiology and the patient's preferences. Antimicrobial therapy should be coherent with the chosen surgical strategy. Level of evidence in the field of PJI is low, and recommendations are based on short literature series, experimental data and expert experience.