This book presents an interesting research where the medical treatment of root canal instrumentation was analyzed with engineering approaches. The structural performances of NiTi endodontic instruments, as well as the impact of geometric parameters, were assessed through finite element method. The canal instrumentation was treated as a material removal process. Engineering principles of metal cutting operations were adapted to accommodate the unique force characteristics of the process, and a physics-based force system was developed which predicts both the torque and the apical force encountered in the process. The fatigue behavior of NiTi instruments was investigated experimentally, and the critical factors were evaluated quantitatively with their impact on the tool's fatigue life. Following the findings, design guidelines were proposed in the aspects of structural performance, cutting forces, and fatigue life. Integrated into a unified system, these guidelines shall help improve instrument design and optimize the mechanical and fatigue performances of endodontic instruments.