In contrast to stem cells of embryonic origin, autologous tissue-specific stem cells are easier to introduce into the clinical practice. In this context however, molecular and cellular changes, which alter tissue-specific stem cell properties with age, are of particular interest, since elderly patients represent the main target group for cellbased therapies. The clinical use of mesenchymal stem cells is an emerging field, especially because this stem cell type appears to be amenable for the treatment of a large number of diseases, such as non-healing bone defects and fractures, inflammatory relieve during arthritis, and the repair of suspensory ligament tears. More than that, mesenchymal stem cells provoke effective immune suppression in the context of graft-versus-host disease. Here, we present a comprehensive overview of the recent findings with special attention to age-related changes of mesenchymal stem cells properties and the consequential impact involved on tissue regeneration and repair, together with the current perception concerning their therapeutic application potential as well as challenges associated with their clinical use.