A traditional concept is that apical periodontitis is the result of pathogenic effects of the microorganisms colonizing the root canal system and the response of the host defence system. The composition of the microflora of root canals differs in primary endodontic treatment and retreatment cases. Persistent disease in the periapical region after root canal treatment presents a more complex situation as it was thought earlier. Scientific evidence indicates that unsatisfactory outcome of cases in which treatment has followed the highest technical standards mainly is associated with microbial factors, comprising extraradicular and/or intraradicular infections.