Conventional endodontic therapy has been shown to be a very predictable (success approximately 90%) treatment for infected pulpal tissue. However, endodontic therapy can occasionally fail. Patients facing this situation typically have many questions regarding the reasons for failure, and are often skeptical regarding additional therapy. While the complexity of a failed endodontic case most often requires the technical skills of a clinician with considerable clinical experience or an endodontist for successful retreatment, the general dentist plays a critical role in the process. This Quality Resource Guide (QRG), using an evidence-based approach, discusses treatment inadequacies that cause endodontic failure, and ways to identify an endodontic treatment failure, determine the potential causes of the failure and assist the patient to determine appropriate steps to address the failure. The QRG also discusses contemporary approaches to retreatment including non-surgical procedures, removal of posts, filling materials and separated instruments, as well as recent evidence of outcomes following apical surgery, intentional replantation and root perforation repair. The QRG is an important reference for the clinician assessing a patient presenting with symptoms that could be related to failed endodontic therapy. It also provides background information for the dental office team to answer patients’ questions regarding potential retreatment options that may be available.