Orthopaedics as a field and a profession is fundamentally concerned with the treatment of musculoskeletal disease, in all of its many forms. Our collective understanding of the cellular mechanisms underlying musculoskeletal pathology resulting from injury continues to evolve, opening novel opportunities to develop orthobiologic treatments to improve care. It is a long path to move from an understanding of cellular pathology to development of successful clinical treatment, and this article proposes to discuss some of the challenges to achieving translational therapies in orthopaedics. The article will focus on challenges that clinicians will likely face in seeking to bring promising treatments forward to clinical practice and strategies for improving success in translational efforts.