Rehabilitation from musculoskeletal injuries is challenging with multiple intrinsic and extrinsic factors influencing athletes, conditions, and length of recovery. Multidisciplinary treatment strategies aim to address pathophysiology, mechanical, and psychosocial factors of injuries. An essential element in the recovery from musculoskeletal injuries is pain control and the return of physiologic function. There have been significant advancements in the understanding of pain and, therefore, new techniques and management strategies are being used. Botulinum neurotoxin (BoNT) has demonstrated valuable biopharmaceutical properties to provide neuromuscular blockade, which, in some cases, can help to return biomechanical and functional physiologic loss. There is developing literature in BoNT's ability to block pain in the treatment of painful musculoskeletal conditions. Critical analysis of the literature is necessary given the paucity of high-quality, evidence-based literature in the treatment of these conditions. This article reviews the utilization of BoNT in chronic exertional compartment syndrome, osteoarthritis, lateral epicondylosis, plantar fasciopathy, and myofascial pain syndrome.