Periprosthetic joint infection (PJI) after total joint arthroplasty is a significant complication, and diagnosis and treatment are challenging, which makes prevention the most compelling strategy. This program defines PJI and explains its incidence, pathogenesis, risk factors, clinical consequences, and financial costs. The implications of biofilm formation for the diagnosis and treatment of PJI are discussed. Preoperative, perioperative, intraoperative, and postoperative preventive strategies are described in detail, focusing on the benefits of irrigation with high-osmolarity surfactant solutions.