The paper is an extensive monographic review of the literature, and also uses the results of the authors’ own experimental research illustrating the noticed developmental tendencies of the filling material based on gutta-percha. The whole body of literature proves the correctness of the research thesis that this material is the best currently that can be used in endodontics. Caries is one of the most common global infectious diseases. Since the dawn of humankind, the consequence of the disease has been the loss of dentition over time through dental extractions. Both tooth caries and tooth loss cause numerous complications and systemic diseases, which have a serious impact on insurance systems and on the well-being, quality, and length of human life. Endodontic treatment, which has been developing since 1836, is an alternative to tooth extraction. Based on an extensive literature review, the methodology of qualifying patients for endodontic treatment was analyzed. The importance of selecting filling material and techniques for the development and obturation of the root canal during endodontic treatment was described. Particular attention was paid to the materials science aspects and the sequence of phase transformations and precipitation processes, as well as the need to ensure the stoichiometric chemical composition of Ni–Ti alloys, and the vacuum metallurgical processes and material processing technologies for the effects of shape memory and superelasticity, which determine the suitability of tools made of this alloy for endodontic purposes. The phenomena accompanying the sterilization of such tools, limiting the relatively small number of times of their use, play an important role. The methods of root canal preparation and obturation methods through cold side condensation and thermoplastic methods, including the most modern of them, the thermo-hydraulic condensation (THC) technique, were analyzed. An important element of the research hypothesis was to prove the assumption that to optimize the technology of development and obturation of root canals, tests of filling effectiveness are identified by the density and size of the gaps between the root canal wall, and the filling methods used and devices appropriate for material research, using mainly microscopy such as light stereoscopic (LSM) and scanning electron (SEM). The most beneficial preparations were obtained by making a longitudinal breakthrough of 48 natural human teeth, extracted for medical reasons, different from caries, with compliance with all ethical principles in this field. The teeth were prepared using various methods and filled with multiple obturation techniques, using a virtual selection of experimental variants. The breakthroughs were made in liquid nitrogen after a one-sided incision with a narrow gap created by a diamond disc using a materialographic cutter. The best effectiveness of the root canal filling was ensured by the technology of preparing the root canals with K3 rotary nitinol tools and filling the teeth with the THC thermoplastic method using the System B and Obtura III devices with studs and pellets of filling material based on gutta-percha after covering the root canal walls with a thin layer of AH Plus sealant. In this way, the research thesis was confirmed.