Despite diligent efforts to prevent infection, prosthetic knee infection occurs in up to 2% of patients treated with total knee arthroplasty. Although the risk of infection is relatively low, the effects are considerable. The number of total knee arthroplasties is projected to increase by more than 600% by 2030, resulting in 3.48 million knee replacements, with a possible 70,000 prosthetic knee infections. Infection will be the most common indication for revision total knee arthroplasty. Prophylactic antibiotics and minimizing patient risk factors are critical in preventing infections. Staphylococcus is the most common organism in infected total knee arthroplasties. Prompt diagnosis and treatment are crucial to the long-term outcomes of patients with prosthetic joint infections. The erythrocyte sedimentation rate, C-reactive protein level, and interleukin-6 serum level should be checked in all patients with clinical signs of infection or unexplained pain or stiffness. The surgical management of a prosthetic knee infection depends on several factors, but none is more important than the timing of infection in relationship to the index surgery. With a success rate of 80% to 90%, two-stage component exchange remains the treatment of choice for chronically infected total knee arthroplasties.