Root canal treatment usually fails when the treatment is carried out inadequately. However, there are some cases in which the treatment has followed the highest standards yet still results in failure. In most of the cases, the endodontic failure results from persistent or secondary intraradicular infection. Extraradicular infections may also be implicated in the failure of some cases. In addition, it has been claimed that a few cases can fail because of intrinsic or extrinsic nonmicrobial factors. The purpose of this paper is to discuss the aetiology of the failure of root canal treatment, particularly in cases of well-treated root canals. Indications for the treatment of endodontic failures are also discussed.