The technical quality of the treatment should always be checked first when problems are encountered in endodontic therapy: for example, working length, coronal seal, and additional canals. These are clearly the most frequent reasons for the lack of a desired response to treatment. The next step is to take a microbiological sample for the analysis and identification of the causative bacteria (or yeasts). The results of this investigation may serve as a basis for the decision of a new treatment strategy. Often in true persistent infections, periapical surgery (apicoectomy) and careful removal and cleaning of the periapical lesion is required for complete healing and a good long-term prognosis.