Periprosthetic joint infection (PJI) after total ankle arthroplasty (TAA) is a dreaded complication that may lead to catastrophic outcomes. Risk factors include a history of surgery on the operated ankle, low preoperative function scores, diabetes, extended surgical time, and postoperative wound-healing problems. Clinical presentation varies and may include increasing ankle pain and swelling, high temperature, local erythema, wound drainage, and dehiscence. The initial diagnostic evaluation should include plain radiographs, erythrocyte sedimentation rate, C-reactive protein levels, and leukocyte count. In suspected cases with elevated erythrocyte sedimentation rate and C-reactive protein, aspiration of the ankle joint for synovial fluid analysis, Gram staining, and culture should be performed. Antibiotic therapy should be based on the pathogen identified, and the surgical strategy should be determined based on the time lines of PJI. Early PJI can be treated with irrigation and débridement with polyethylene exchange. The surgical treatment of choice for late PJI is two-stage revision arthroplasty, which includes removal of the implant, insertion of an antibiotic spacer, and reimplantation of a TAA. In certain chronic PJI cases, permanent articulating antibiotic spacers can be left in place or an ankle arthrodesis can be performed. Below-knee amputation is considered as the final option after limb-sparing procedures have failed.