While one of the major achievements of the 20th century was prolonging life expectancy in developed countries, the main challenge of the 21st century is to improve the quality of life of the aging population. Aging is associated with a progressive reduction of organ system function. Therefore, regenerative medicine will be one of the major developing fields of medicine. This new medical field does not only apply to aging but also to all degenerative diseases, such as arthritis and degenerative joint disease, which lead to progressive degeneration of mesenchymal tissues such as bone and cartilage. The discovery of pluripotent mesenchymal stem cells (MSCs) offers a promising alternative to surgery for non-invasive regenerative therapies of mesenchymal tissues. This review focuses on the characterization and potential application of MSCs in the regeneration of damaged joints.