Background: Inability to recognize anatomical variations in roots and canal configurations remains one of the principal factors in failure of endodontic therapy. Mandibular premolars, due to their varied internal morphology, present an endodontic challenge more often than other teeth. Objective: To assess the root morphology and canal configuration of mandibular first and second premolars using three-dimensional cone-beam computed tomography imaging (3D CBCT). Methodology: Bilaterally, mandibular premolars were evaluated on 100 CBCT images independently by two experienced endodontists. Vertucci's classification was used to identify and divide the canal configurations. Results: 97% of first premolars and 99.5% of the second premolars were found to have one root. The most common canal configuration was found to be Type-I. Other types of canal configurations were 5.5% and 5% in first and second premolars respectively. Conclusions: Modern-day endodntist needs to be vigilant at all times to avoid missing canals and consequent failures.