Successful endodontic treatment depends largely on the effective elimination of microorganisms from the root canal system. Conventional chemomechanical preparation significantly reduces microbial load; however, the complex anatomy of root canals often prevents complete disinfection. Persistent microorganisms, particularly Enterococcus faecalis, remain a major cause of endodontic treatment failure. Recent advances in root canal disinfection techniques have focused on improving irrigation efficacy, enhancing antimicrobial activity, and overcoming anatomical challenges. Innovations such as passive ultrasonic irrigation, laser-activated irrigation, photodynamic therapy, ozone therapy, nanoparticle-based disinfectants, multisonic irrigation systems, and regenerative endodontic protocols have significantly enhanced root canal decontamination. This review examines contemporary advances in root canal disinfection, evaluates their mechanisms of action, clinical effectiveness, advantages, limitations, and future developments. Current evidence suggests that advanced disinfection technologies improve microbial reduction, biofilm disruption, and treatment outcomes while supporting minimally invasive and biologically driven endodontic approaches.