The progression of rheumatoid pathologies, degenerative diseases, traumatologies, and their cortege of increasing medical, social and economical needs, has mandated the development of tissue repair and engineering technologies in orthopedic medicine. Mesenchymal stem cells (MSCs) are multipotent cells that can be extracted from large and relatively easily accessible compartments of the body, especially the bone marrow, and such cells are able to differentiate into adipogenic, chondrogenic and osteogenic precursors. The concept of using MSCs to repair tissues has progressively evolved, and the goal of cell-mediated therapy is to prolong the natural physiological abilities of healing, or substitute them, when these are lacking, failing or progressing too slowly. In recent years, the first clinical trials on the utility of MSCs, with or without scaffolds and/or growth factors, have been initiated. In this review, the authors focus on findings from preclinical research, clinical trials and case reports involving bone and cartilage repairs. New perspectives are considered regarding uses of cell types, cell delivery approaches and growth factors. They also consider the stringent conditions, constraints and considerations necessary to take cell-mediated therapy from bench to bedside.