The root canal system is complicated and has many anatomical variations among different populations. It is so important to understand the morphology of root canal system before any endodontic procedure, since the lack of knowledge of root canal system could lead to missing the additional root canals which causes failure of endodontic treatment. The study of root canal anatomy was carried out by many researchers and among different populations using various techniques. The presence of additional root canals was most commonly observed in molars. The aim of this chapter is to provide an overview of the morphology of root canal system of maxillary and mandibular molars and its variation among populations.