Melcher established that if PDL cells are given preference, regeneration may consistently occur. Bone grafts, though considered “gold standard”, bone regeneration after grafting is quite variable. 21st century appears to represent a time in history when there is a convergence between clinical dentistry and medicine, human genetics, developmental... Growth/differentiation factors in spite of their promise of revolutionizing field of bone regeneration must be used at very high concentrations to be effective and also they do not induce long-term changes in the diseased tissue. Healing of periodontal wounds is a more complex process. Current regenerative therapies include bone grafts, allogenic and xenograft bone matrix, root conditioning agents and cell-occlusive barrier membranes and, most recently, recombinant growth/differentiation factors. The novel approach would include changes at a genetic level to modify the disease process for long-term beneficial effects of regenerative molecules.