Despite biologic evidence showing that regeneration can occur in humans, complete and predictable regeneration still remains an elusive clinical goal, especially in advanced periodontal defects. The isolation and characterization of stem cells from periodontal tissues have provided a good starting point for understanding the role of progenitor cells in periodontal healing. However, we have an incomplete understanding of the way the roots develop, and little is known about the signaling mechanisms that occur during this process. It is unclear whether human stem cell derivatives can integrate into recipient tissue and fulfill the specific functions of lost or injured tissues. It will be necessary to demonstrate that stem cells develop into stable cells and display the characteristics and functions of normal host cells following their transplantation. It is hoped that the knowledge on stem cells, growth factors, and delivery systems, will someday make stem cell therapy an effective and safe approach in periodontal regeneration.