Tooth loss is strongly associated with the occurrence of several comorbidities and social well-being problems, mainly among children and young people. These individuals may have the process of tooth development impaired by microbial invasion caused by untreated dental caries, traumatic injuries, and/or dental anomalies. Although conventional endodontic treatment was considered the treatment of choice for necrotic teeth for many years, regenerative endodontic procedures (REPs) has become a paradigm shift in the treatment of young permanent teeth with pulp necrosis and an open apex. REP is a biologically based procedure, which has gained popularity among many researchers and clinicians and involves the three classic principles of tissue engineering (stem cells, signaling molecules, and a 3-dimensional scaffold), in addition to the need for efficient bacteria control within the root canal system. In addition to promoting pain resolution and the preservation of the remaining tooth structure, this approach aims to allow continued development and regeneration of the root and surrounding damaged tissues of necrotic young permanent teeth. Despite the absence of a standard irrigation protocol available in REPs, the ideal protocol should be based on microbiological and immunological principles, eliminating biofilm and enhancing growth factor release to favor stem cell proliferation and differentiation. Furthermore, clinicians should choose adequate scaffold materials to induce the formation of mineralized tissue in the weakened dentinal walls and ensure an optimum environment for tissue regeneration or repair. The search for appropriate strategies over the years to recreate the most ideal regenerative niche, evaluating different biomimetic cell-friendly protocols and materials to optimize the outcomes of REPs, is to be foreseen in the future. Thus, this book addresses the biological basis of tissue regeneration, clinical indications, current clinical protocols, the most suitable biomaterials used in REPs, the characteristics of clinical success, and the management of treatment failure, as well as the future perspectives of REPs in Endodontics.