Persistent apical periodontitis occurs when multiple root canal treatments fail to adequately eliminate intraradicular infection due to chronic apical periodontitis. Extraradicular infections play an unequivocal role as causative agents of persistent apical periodontitis, which is characterized by extraradicular biofilms and other bacterial colonies in the periapical lesion. This review highlights the relationship between extraradicular biofilms and persistent apical periodontitis. In addition, the profiles, structure, microbial composition, and elimination methods of extraradicular biofilms are summarized.