Deep infection is a devastating complication following total knee arthroplasty. Prompt diagnosis and definitive treatment of this complication are essential for a successful outcome. The treatment options for an infected total knee replacement include (1) antibiotic suppression alone; (2) aggressive wound debridement, drainage, and antibiotic suppression therapy; (3) resection arthroplasty; (4) arthrodesis; (5) two-stage reimplantation; and (6) amputation. Successful salvage of this complication can be accomplished only by extensive investment of surgical and infectious disease efforts in eradicating the infection. Two-stage reimplantation has been the most successful functional option and should be used whenever possible to definitively eradicate the infection and ensure good function of the knee joint.