BACKGROUND: Mesenchymal stem cells (MSC) are multipotent cells with the ability to differentiate into mesenchyme-derived cells including osteoblasts and chondrocytes. OBJECTIVE: To provide an overview and expert opinion on the in vivo ability of MSC to home into tissues, their regenerative properties and potential applications for cell-based therapies to treat bone and cartilage disorders. METHODS: Data sources including the PubMed database, abstract booklets and conference proceedings were searched for publications pertinent to MSC and their properties with emphasis on the in vivo studies and clinical use in cartilage and bone regeneration and repair. The search included the most current information possible. CONCLUSION: MSC can migrate to injured tissues and some of their reparative properties are mediated by paracrine mechanisms including their immunomodulatory actions. MSC possess a critical potential in regenerative medicine for the treatment of skeletal diseases, such as osteoarthritis or fracture healing failure, where treatments are partially effective or palliative.