Endodontic treatment aims to eliminate microorganisms from the root canal system to prevent reinfection. Chemo-mechanical preparation-combining mechanical instrumentation with chemical irrigation-is crucial for removing pulp tissue, bacteria, and debris. However, persistent microbes, especially in the apical region where anaerobic biofilms thrive, can lead to treatment failure and apical periodontitis. Biofilms are resistant due to complex canal anatomy, making them difficult to remove completely. Scanning electron microscopy shows deep bacterial penetration into dentinal tubules, highlighting the challenge of full disinfection. Even after thorough cleaning, bacteria may persist in inaccessible areas. To improve outcomes, advanced irrigation and agitation systems have been developed to enhance disinfectant penetration and effectiveness, especially in complex canal structures like isthmi and fins. This book highlights various endodontic irrigants, advanced irrigant delivery and agitation systems to attain maximum potential of chemo-mechanical debridement in complex root canal system.