Musculoskeletal disease is prevalent in society and with an ageing population, the incidence and impact on public health are set to rise. Severe long-term pain and mobility restriction impair the welfare and quality of life of patients with musculoskeletal disease. Current treatments are often restricted to the management of symptoms or temporary replacement with inert materials, rather than targeting prevention and cure. There is an urgent need for alternative biological approaches to musculoskeletal disease therapy. The rapid emergence of stem cell technologies, primarily using ‘mesenchymal stem cells’ (MSCs), has resulted in a number of pre-clinical and clinical studies in an effort to provide more effective treatment options. Challenges exist in bench-to-bedside translation, but they are not insurmountable.