Regenerative endodontic procedures aim to form a vital tissue into an empty but infected root canal space that restores the lost functions of the native dental pulp. These procedures have been shown to promote healing of apical periodontitis and further root development by the deposition of hard tissue and continued root development in immature permanent teeth with necrotic pulp and apical periodontitis/abscess. Although these procedures appear to achieve desirable clinical outcomes, there is increasing evidence that the tissues formed following these procedures do not resemble the lost native pulp. In this presentation, new histologic observations will be provided, demonstrating that the mineralized tissue formed following pulp capping or pulpotomy procedures, as well as the tissue formed in the root after regeneration procedures, is not tubular dentin formed by a new generation of odontoblast-like cells, but rather an irregular amorphous mineralized tissue showing cellular inclusions. The clinical and scientific meaning of clinical versus histologic outcomes will be presented and discussed with focus on current technical and scientific challenges and possible future directions.