Since antiquity, wounds of all varieties have been the result of trauma, infection and vascular or autoimmune disorders. The intentional surgical wounding of a tissue is a dynamic process which elicits a complex and dynamic response in the tissue that has been injured.The healing of a wound includes the various phases of blood clotting, wound cleansing, tissue formation, tissue modeling and remodeling. These phases occur in an orderly sequence but, in a given site, may overlap in such a way that in some areas of the wound, tissue formation may be in progress while in other areas tissue modeling is the dominating event. Current scientific evidence points to the presence of cells originating from the periodontal ligament, wound stability, space provision, and primary intention healing, as fundamental biologic and clinical factors that must be met to obtain periodontal regeneration. Only a profound understanding of biological and clinical variables affecting the outcome of periodontal- regenerative procedures will allow clinicians to manipulate biological and clinical factors effectively in order to optimize the clinical result and increase the predictability of periodontal surgery.