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Centrally acting skeletal muscle relaxants (CASMR) are widely prescribed as adjuncts for acute and chronic pain. Given the recent interest in multimodal analgesia and reducing opioid consumption, there has been an increase in its use for perioperative/postoperative pain control. The mechanism of action, pharmacodynamics, and pharmacokinetics of these drugs vary. Their use has been studied in a wide range of operative and non-operative settings. The best evidence for the efficacy of CASMRs is in acute, nonoperative musculoskeletal pain and, in the operative setting, in patients undergoing total knee arthroplasty and abdominal surgery, including inguinal herniorrhaphy and hemorrhoidectomy. The risk of complications and side effects, coupled with the limited evidence of efficacy, should prompt careful consideration of individual patient circumstances when prescribing CASMRs as part of perioperative pain management strategies.