Endodontic challenges relating to root canal morphology are critical problems in everyday dental practice. The complexity and variability of the root canal system present significant difficulties in effective cleaning, shaping, and obturation. Variations in canal anatomy, such as accessory canals, bifurcations, and intricate curvatures, complicate the debridement process and may leave infected tissue or debris behind. Moreover, these anatomical irregularities can lead to procedural errors during instrumentation. Advanced imaging techniques, such as cone-beam computed tomography, have enhanced the detection of complex canal morphologies, allowing for more precise treatment planning. However, the clinician’s ability and experience remain critical in addressing these anatomical obstacles. The development and application of flexible nickel-titanium instruments have greatly improved the ability to navigate and shape complex canal systems. Despite these advances, the unpredictability of root canal morphology remains the most important factor influencing the success rate of endodontic treatments. The following chapter provides guidelines for addressing the challenges that morphology presents to the clinician.