Periodontal regeneration refers to healing after periodontal surgery that result in the restoration of the lost periodontium and attachment apparatus viz. cementum, alveolar bone and periodontal ligament. 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. A significant issue will be finding ways to identify and maintain multipotential stem cells in vitro. The growth and differentiation conditions that induce lineage specific commitment will be needed to be established. In addition, suitable integrate into the surrounding environment for the reconstruction of functional complex organ systems will need to be developed. It is expected that a multilevel approach involving cell biologists, matrix biologists, pharmacologists, biomaterials scientists / engineers and nanotechnologies will be required to address many of these issues.