Diverse technologies have emerged in recent times to streamline applications of more predictable materials and methods, in order to attain the elusive goal of periodontal regeneration. Their applications, current limitations and future directions are reviewed. In addition to grafting materials and barrier membranes to exclude epithelial downgrowth and promote mesenchymal elements, the environment of the cell is pivotal to events that follow. These include application of scaffolds, lasers, harnessing bone anabolic activity and the resolution of inflammation using cell-and gene-based protein and peptide therapy. Recommendations embrace suitable targets for patient outcome based on clinical applications of scientific principles for more predictable and consistent results in regenerating hard and soft tissues of a functional periodontium. They must, however, stay within safety requirements and an effective cost/benefit ratio. Regenerative medicine and dentistry combine applications of molecular biology, material science, bioengineering and nanoscience in order to repair, regenerate and replace missing tissue. The author discusses these applications as well as the mechanisms that modulate cells and matrices in periodontal regeneration as well as regenerative medicine.