The prospect of improved regeneration is not only the promise held out by stem cell research, critical studies of unique aspects of early human development are now within reach with the use of embryonic stem cells. Although our understanding of the molecular pathways underlying mesenchymal stem cells differentiation is expanding, translation of this knowledge into tissue engineering strategies remains in its infancy. In the context of orofacial tissue engineering, populations of stem cells that form bone, cementum; dentin and even periodontal ligament have been identified. This has unlocked a new direction of research to restore the form and function of the oral cavity using autologous cells, thereby preventing histocompatibility mismatch and transmission of disease. With the first reports of adult human stem cell populations residing in the periodontal ligament beginning to emerge, the next phase will be to determine the clinical utility of these cells. Accordingly, further studies are now required to determine the efficacy of ex vivo expanded stem cells to repair periodontal defects.