Root canal treatment (RCT) aims to eliminate bacteria and infected tissues, restore tooth function, and ensure long-term prognosis. Advances in microscopic endodontics and nickel-titanium (NiTi) files have significantly enhanced RCT success rates by improving canal shaping and minimizing procedural errors. However, clinical failures still occur, primarily categorized as biological or mechanical. Biological failures, such as missed canals or inadequate obturation, can often be managed through retreatment or surgical intervention. In contrast, mechanical failures, including apical cracks and vertical root fractures (VRF), pose greater challenges and are often irreversible. NiTi files, valued for their superelasticity and flexibility compared to stainless-steel instruments, can inadvertently induce stress concentrations in root dentin and the files themselves due to their metallic properties and memory effect. Over-instrumentation, in particular, increases the risk of apical cracks that may progress to VRFs under functional loading. Stress generation during instrumentation is influenced by file geometry, kinematics, and alloy composition. Designs with smaller cross-sectional areas, reduced pitch, and heat-treated alloys have demonstrated reduced screw-in forces and stress generation, while reciprocating motion mitigates cyclic fatigue and apical stress compared to continuous rotation. Innovative file designs, such as off-centered and self-adjusting files, have further reduced stress concentrations and dentinal defects. Nonetheless, operator techniques, including maintaining precise working length and controlled pecking depth, remain critical for minimizing stress and preventing mechanical failures. In conclusion, understanding the mechanical properties of NiTi systems and implementing evidence-based strategies are essential for minimizing complications and ensuring favorable RCT outcomes.