While infection in TKA is a relatively infrequent complication, it can be devastating in terms of morbidity and cost. Prevention of infection begins with patient selection. Prior knee sepsis surgery, rheumatoid arthritis, and poor general health may lead to an increased rate of infection. Prophylactic antibiotics, meticulous surgical technique, and control of the intraoperative environment have been shown to be beneficial in prevention of infection after TKA. Diagnosis can be difficult and often is heralded by the onset of pain in a previously pain-free knee. Aspiration is an excellent screening tool and is also beneficial in determining management of potentially infected TKAs. In cases posing a diagnostic dilemma, radiographs and nuclear medicine studies also may prove beneficial as well as intraoperative frozen section. Management is based on chronicity of the infection and fixation of the components. Antibiotic suppression is unlikely to yield a cure but may be indicated in the medically infirm. Debridement with component retention may be used with varying degrees of success, especially in the acute postoperative period. The current treatment of choice for chronic infections in this country is a two-stage revision with interim intravenous antibiotics. This would be expected to yield a cure in approximately 80% of patients. Arthrodesis may be necessary in the patient who is status post-multiple revisions with particular virulent organisms. Resection arthroplasty should be reserved for the older rheumatoid patient with limited functional demands. Finally, amputation should be considered in the patient with life-threatening sepsis or the patient who is status post-multiple revisions with intractable pain and poor bone stock.