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Regenerative endodontic procedures for immature permanent teeth with apical periodontitis confer biological advantages such as tooth homeostasis, enhanced immune defense system, and a functional pulp-dentin complex, in addition to clinical advantages such as the facilitation of root development. Currently, this procedure is recognized as a paradigm shift from restoration using materials to regenerate pulp-dentin tissues. Many studies have been conducted with regard to stem/progenitor cells, scaffolds, and biomolecules, associated with pulp tissue engineering. However, preclinical and clinical studies have evidently revealed several drawbacks in the current clinical approach to revascularization that may lead to unfavorable outcomes. Therefore, our review examines the challenges encountered under clinical conditions and summarizes current research findings in an attempt to provide direction for transition from basic research to clinical practice.