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The goal of endodontics is to save teeth. Since inception, endodontic treatments are performed to obturate disinfected root canals with inert materials such as gutta-percha. Although teeth can be saved after successful endodontic treatments, they are devitalized and therefore susceptible to reinfections and fractures. The American Association of Endodontists (AAE) has made a tremendous effort to revitalize disinfected immature permanent teeth in children and adolescents with diagnoses including pulp necrosis or apical periodontitis. The American Dental Association (ADA) in 2011 issued several clinical codes for regenerative endodontic procedures or apical revascularization in necrotic immature permanent teeth in children and adolescents. These AAE and ADA initiatives have stimulated robust interest in devising a multitude of tissue engineering approaches for dental pulp and dentin regeneration. Can the concept of regenerative endodontics be extended to revitalize mature permanent teeth with diagnoses including irreversible pulpitis and/or pulp necrosis in adults? The present article was written not only to summarize emerging findings to revitalize mature permanent teeth in adult patients but also to identify challenges and strategies that focus on realizing the goal of regenerative endodontics in adults. We further present clinical cases and describe the biological basis of potential regenerative endodontic procedures in adults. This article explores the frequently asked question if regenerative endodontic therapies should be developed for dental pulp and/or dentin regeneration in adults, who consist of the great majority of endodontic patients.