Pain after total knee arthroplasty (TKA) is not infrequent and may be indicative of a broad spectrum of prosthesis-related, intra-articular, or extra-articular pathologies. To diagnose and treat the underlying cause of a painful TKA, systematic evaluation of the patient is critical to ensure that they are managed appropriately and expeditiously. This evidence-based review presents current concepts regarding the pathophysiology, etiology, and diagnosis of painful TKA and our recommended approach for management. [Orthopedics. 2021;44(6):341-352.].