Endodontic treatment failure is usually characterised by the presence of post-treatment apical periodontitis, which may be persistent, emergent or recurrent. Understanding the causes of endodontic treatment failure and making a correct diagnosis are of paramount importance for the proper management of this condition. In clinical practise, endodontic treatment failure is mainly related to the poor quality of root canal treatment (RCT), the nature of the disease and the concomitant disease of the tooth. This article focuses on the above three factors and discusses the indications and basics of the procedures for optimal clinical management of this condition.