It is well established that the periodontally diseased root surface does not favor regeneration of the periodontium due to its surface characteristics. Demineralization has been shown to alter the diseased root surface, creating a more acceptable surface that can influence events in wound healing. The in vivo and in vitro studies clearly indicate a greater potential for cell and fiber attachment to demineralized root surfaces. Other factors such as spatial relationships and wound stabilization may also impact the extent and predictability of periodontal wound healing following root surface demineralization. Appropriate root surface conditioning may, therefore, regulate the adsorption of plasma proteins, enhance adhesion of the blood clot and stimulate deposition of collagen against the root surface. An understanding of the early events in wound healing, therefore, appears critical to the selection of appropriate agents and their potential to promote regeneration.