Advances in implant design, surgical technique, peri-operative antimicrobial prophylaxis and laminar airflow operating room environment have made total joint arthroplasty one of the most successful surgical procedures of all times. Orthopaedic implants, however, remain prone to microbial contamination resulting in persistent risk of implant-associated infection. Treatment of infections associated with orthopaedic devices usually requires appropriate surgical intervention combined with a prolonged antimicrobial therapy. The choice of the best possible treatment regimen depends on duration and pathogenesis of infection, stability of the implant, antimicrobial susceptibility of the pathogen and condition of the surrounding soft tissue. In addition towell known diagnostic procedures new promising tools for rapid and correct microbial diagnosis are being developed as correct diagnosis of the responsible micro-organism and this is paramount for successful treatment of prosthetic joint infection.