Despite the fact that patients present with endodontic-periodontal combined lesions are commonly seen, clinical dilemma is frequently brought up due to the difficulties in differential diagnosis and prognosis prediction. Such difficulties can be reconciled by proper diagnosis of each specific lesion, and such diagnosis can only be made through acknowledging the cause of each lesion and the interrelationship between endodontic and periodontal diseases. This article is an attempt to focus on appraising the causes and contributing factors of endodontic-periodontal lesions as well as the connections between pulpal and periodontal tissues, and to provide a rationale to diagnosis, prognosis, and treatment of these conditions.ope