The human periodontium and dental pulp cavity are closely connected by their proximity and by the presence of apical and lateral radicular foramina, which permit the passage of pathogens between these two distinct anatomical areas. The interrelationship of these structures influences each other during health, function and disease. Although there are many factors that contribute to the development and progression of endodontic and periodontal diseases, the primary cause of both diseases is the presence of bacterial infections with complex microbial ﬂora. Etiologic factors such as bacteria, fungi, and viruses as well as other various contributing factors such as trauma, root resorptions, perforations, and dental malformations also play an important role in the development and progression of such lesions. Although disease transmission from the pulp to the periodontal tissue is possible, the influence of periodontal disease on pulpal status remains controversial. The differential diagnosis of endodontic and periodontal diseases can sometimes be difficult but it is of vital importance to make a correct diagnosis so that the appropriate treatment can be provided. Endodontic-periodontal lesions present challenges to the clinician as far as diagnosis and prognosis of the involved teeth are concerned.