Musculoskeletal pain is a common healthcare burden, and is often managed with oral pain relief medications. When used recurrently or long-term, such medications can present adverse effects and tolerability concerns. Recent research on the endocannabinoid system and cannabinoid receptors has opened a new avenue in pain management. Cannabinoids such as Cannabidiol (CBD) and others from the leaf extract of Cannabis sativa, can be administered as topical oils, creams and gels, and be a useful alternative and adjunct in the management of chronic musculoskeletal pain. Cannabinoids act via multiple receptors and pathways to reduce pain transmission and perception. Early pre-clinical and clinical evidence has shown the efficacy, safety and tolerability of topical cannabinoids in arthritis pain, back pain, myofascial, and neuropathic pain. Larger and a greater number of clinical studies as well as real-world evidence can add further insights.