Human bone marrow-derived mesenchymal stem cells (MSCs) can self-renew and differentiate into osteoblasts, chondrocytes, and adipocytes. MSCs have effectively emerged as a promising tool for clinical applications, specifically in musculoskeletal diseases. This article reviews the status of preclinical animal studies, clinical trials, and the efforts of the industry in using MSCs to treat musculoskeletal diseases such as bone fractures, bone defects, focal chondral lesions, osteoarthritis, spinal diseases, and tendon injuries. We also discuss the current problems encountered and potential of using MSCs in future clinical studies.