The number of total ankle replacements (TARs) performed in the United States has dramatically increased in the past 2 decades due to improvements in implant design and surgical technique. Yet as the prevalence of TAR increases, so does the likelihood of encountering complications and the need for further surgery. Patients with new-onset or persistent pain after TAR should be approached systematically to identify the cause: infection, fracture, loosening/subsidence, cysts/osteolysis, impingement, and nerve injury. The alignment of the foot and ankle must also be reassessed, as malalignment or adjacent joint pathology can contribute to pain and failure of the implant. Novel advanced imaging techniques, including single-photon emission computed tomography and metal-subtraction magnetic resonance imaging, are useful and accurate in identifying pathology. After the foot and ankle have been evaluated, surgeons can also consider contributing factors such as pathology outside the foot/ankle (eg, in the knee or the spine). Treatment of the painful TAR is dependent on etiology and may include debridement, bone grafting, open reduction and internal fixation, realignment of the foot, revision of the implants, arthrodesis, nerve repair/reconstruction/transplantation surgery, or, in rare cases, below-knee amputation. Level of Evidence: Level V, expert opinion or review.