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During the last few decades, many new instruments and materials have been developed and introduced to the market. Along with these innovations, new, more clinically appealing, and promising techniques of root canal cleaning, shaping, and obturation were introduced to increase the success rates of endodontic treatment and retreatment, and the survival of endodontically treated teeth. This Special Issue of the Journal of Functional Biomaterials will cover different topics of new biomaterials developed for endodontic application: materials for the disinfection/irrigation of the root canal system, temporary and permanent endoaccess and root canal filling, the management of endodontic complications, regenerative endodontics, or endodontic surgery.