The etiology of vertical root fractures (VRFs) in endodontically treated teeth is complex because of its multifactorial nature. Since there is no single specific etiology that is pathognomonic for this complication that can be identified, prevention of vertical root fractures in endodontically treated teeth is quite difficult. There are predisposing factors as well as contributing ones. The predisposing factors are practically noncontrollable. These include the specific anatomy of the susceptible roots, biochemical changes in the root dentin in the endodontically treated tooth, and loss of healthy tooth substance as a result of caries and trauma before beginning endodontic procedures. The contributing factors are attributed to the iatrogenic risk factors associated with various dental procedures performed on the tooth. These clinical etiologies will be discussed in the first section, and a fracture mechanics perspective will be presented in the second section. This will incorporate geometry, material, and loading issues when a dentinal crack is initiated in the canal wall, which is a precursor for a future complete and incomplete fracture in the root at a later stage.