Aim: One of the main objectives of root canal treatment is disinfection of the root canal system. However, this goal is hampered by complex root canal anatomy. Practitioners should be familiar with the morphology of the roots of all the teeth and the associated intricate root canal anatomy for effective debridement, disinfection and obturation to be achieved. This article presents the successful management of two maxillary first molars with two canals in a single and separate distobuccal root and reviews the available literature on root canal configurations of single and separate distobuccal roots of maxillary molars. Materials and methods: Nonsurgical root canal treatment of two maxillary first molars was performed with the aid of a dental operating microscope and cone beam computed tomography. The literature review was conducted using the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed). Results: The overall incidence of two-canalled distobuccal roots in maxillary molars ranged from 1.0% to 2.3%. The most common root canal configurations found in clinical/laboratory studies were Vertucci type IV (2-2) and type II (2-1). In clinical case reports, Vertucci type II (2-1) was the most common configuration. The incidence of three-canalled distobuccal roots was found to be 0.72% only. Clinicians should always keep in mind the high complexity of the root canal system. All possible efforts should be made to locate and treat root canal variations to enhance the prognosis of endodontic treatment. Keywords: disinfection, distobuccal root, maxillary first molar, root canal variations