Public interest in the analgesic potential of cannabinoids has grown, but there is no consensus regarding orthopedic applications. Available evidence was identified for cannabinoid use in arthritis, neuropathic pain, fibromyalgia, multiple sclerosis, and postoperative pain. Extracted information included the risks of preoperative use, associations with opioid dependence, and surgical complications. There is limited evidence for therapeutic benefit of cannabinoids in rheumatoid arthritis and fibromyalgia. Cannabinoids are not indicated for postoperative pain. Preoperative unregulated use has been linked with postoperative opioid dependence. Cannabinoids may be considered a second- or third-line treatment for analgesia for some orthopedic pathologies. [Orthopedics. 2022;45(4):e183-e189.].