Experimental studies have shown that the potential of periodontal regeneration seems to be limited by the regenerative capacity of the cells involved. The regeneration of damaged periodontal tissues is mediated by various periodontal cells and is regulated by a vast array of extracellular matrix informational molecules that induce both selective and nonselective responses in different cell lineages and their precursors. In this paper, we first review periodontal ligament tissue and its different cell subpopulations including fibroblasts and paravascular stem cells, and their functions during the development and homeostasis of periodontal tissues. Because conventional periodontal regeneration methods remain insufficient to obtain a complete and reliable periodontal regeneration, the concept of periodontal tissue engineering has been based on the generation of the conditions necessary to improve the healing of periodontal tissues. Additionally, the potential of periodontal ligament cells for use in periodontal tissue engineering to overcome the limitations of conventional periodontal regenerative therapies is discussed, followed by an update of the recent progress and future directions of research utilizing periodontal ligament cells for predictable periodontal regeneration.