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The subspecialty of regional anesthesiology and acute pain medicine (RAAPM) is in a position to lead changes that may impact the current opioid crisis. At the hospital level, RAAPM experts can implement evidence-based multimodal analgesic clinical pathways featuring regional anesthesia. Multimodal analgesia consists of using two or more analgesic modalities targeting pain pathways at various levels to improve pain control, while also aiming to reduce opioid utilization and related adverse effects. These types of pathways or protocols have been widely applied in the joint replacement population. This review focuses on the current state of the evidence regarding individual elements of a multimodal analgesic pathway for patients with total knee arthroplasty including new regional anesthesia techniques like the IPACK (Infiltration between the Popliteal Artery and Capsule of the Knee) block and suggests future research directions to improve the clinical care of this surgical population in the future., (Published by Elsevier Ltd.)