This review outlines the biological basis and clinical protocols used currently in regenerative endodontic procedures and discusses future directions in pulp regeneration appraches. Since the discovery of dental stem cells capable of differentiating into odontoblast-like cells and revascularization/regenerative endodontic therapy with the potential of promoting thickening of the canal walls and continued root development of immature permanent teeth with necrotic pulps, the study of pulp tissue engineering or pulp tissue regeneration has taken a giant step forward in biological and clinical endodontics. The biological concept of regenerative endodontics involves the triad of stem cells, scaffold, and signaling molecules. In preclinical studies, researchers are looking for mesenchymal stem cells not only capable of differentiating into odontoblast-like cells but also highly angiogenic/vasculogenic and neurogenic for complete pulp regeneration. Tremendous efforts are also dedicated to search for three-dimensional biomimetic scaffolds to enhance stem cell migration, adhesion, proliferation, and differentiation as well as tissue structure support. In clinical trials, besides immature permanent teeth with necrotic pulp, regenerative endodontic therapy has been employed to treat mature permanent teeth with necrotic pulps, teeth with persistent apical periodontitis after primary root canal therapy, and traumatized teeth associated horizontal root fractures, root resorption, and avulsion.