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As surgical techniques and pharmacology advance, the management of postoperative pain in patients undergoing total knee arthroplasty (TKA) continues to evolve. The current standards of care are composed of multimodal pain management including opioids, nonsteroidal anti-inflammatory drugs and gabapentinoids, peripheral nerve blocks, and periarticular injections. Newer modalities are composed of delayed release local anesthetics and cryoneurolysis. To summarize the current evidence-based treatment modalities and forecast changes in the management of patients having TKAs, we reviewed available data on: (1) oral analgesics; (2) periarticular injections; (3) peripheral nerve blocks; (4) multimodal regimens; and (5) newer modalities in post-TKA pain management. Multimodal analgesic regimens that target numerous pain pathways may provide the best pain management, rehabilitation, patient satisfaction, and reduce opioid use and related side effects. Periarticular injections of delayed-release local anesthetics may further enhance pain management.