In addition to stabilizing osteosynthesis and autologous bone transplantation, so-called orthobiologics are playing an increasing role in the treatment of bone-healing disorders. Besides the application of different growth factors, new data in the literature suggest that cell therapeutic agents promote local bone regeneration. Due to ethical and biological considerations, clinical application of progenitor cells for the musculoskeletal system is limited to autologous postpartum stem cells. Here in particular, cell therapy with autologous progenitor cells in one surgical session has delivered first promising results. Based on a review of the literature and on our own experience with 75 patients, this article reviews the rationale and characteristics of the clinical application of cell therapy for the treatment of bony substance defects. Most clinical trials report successful bone regeneration after the application of mixed cell populations from bone marrow.