Musculoskeletal disorders represent the fourth most common cause of disability, following neuropsychiatric disorders, neoplasms, and cardiovascular disease in both developed and developing countries. These injuries include a variety of disorders that cause pain in bones, joints, muscles, or surrounding structures. Musculoskeletal pain is a known consequence of repetitive strain, overuse, and work-related physical disorders. Pain can be acute or chronic, focal or diffuse, and associated with worse functional outcomes and poorer quality of life when compared to a range of other chronic conditions. The pathophysiology of musculoskeletal pain is not completely clear and the repertoire of analgesics available is limited. Osteoarthritis and, to a lesser extent, rheumatoid arthritis are considered as the most common of the articular disorders and are frequently cited as the leading cause of persistent musculoskeletal pain. Inflammation, fibrosis, tissue degradation, and neurosensory disturbances have all been implicated in the induction, sensation and maintenance of chronic arthritic joint pain. Several preclinical models of musculoskeletal pain have been developed to better understand the mechanisms that drive different types of musculoskeletal pain and the development of new analgesics that could have significant clinical, economic and societal benefits.