As the number of primary total ankle replacements increases for treatment of end-stage ankle arthritis, failures are also expected to rise. Periprosthetic joint infection is among the causes of failures and has been reported to be as high as 5%. Diagnosis is usually made by a combination of clinical examination findings, imaging, laboratory, and microbiological workup. Management is generally separated into limb salvage or amputation. Limb salvage can be challenging and may involve a single versus staged approach. Options include revision arthroplasty or arthrodesis procedures (ankle versus tibiotalocalcaneal), and a multidisciplinary approach is sought to eradicate infection before definitive management.