Stem cells have for many years been gaining interest in the context of their potential applications in the tissue engineering-based treatment of musculoskeletal disorders. What made them such an attractive topic was that mesenchymal stem cells (MSCs) are capable of differentiating into one of several mesenchymal phenotypes such as osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon-ligament fibroblasts, and adipocytes. However, it seems that their most promising activity is a trophic effect on surrounding cells and tissues. MSCs secrete bioactive factors that suppress the local immune system; inhibit fibrosis, scar formation, and apoptosis; enhance angiogenesis; and stimulate mitosis and differentiation of tissue-intrinsic reparative or stem cells. MSCs respond to inflammation and fibrotic environment and control nociceptive pathways. Trophic and immunomodulatory behaviour of mesenchymal stem cells can be effectively used in tissue reconstruction based on cell transplantation. In these situations, MSCs possibly help other cells and protect against a hostile environment at the site of damage. In this approach, MSCs should be perceived in a different way than previously, which assumed that they are the building blocks of new tissue, or rather become a powerful tool in tissue regeneration, as cells supervising and supporting by organising the ideal environment for tissue regeneration.