The actual relationship between periodontal and pulpal disease was first described by Simring and Goldberg in 1964. Since then, the term “perio-endo” lesion has been used to describe lesions due to inflammatory products found in varying degrees in both the periodontium and the pulpal tissues.Endodontic–periodontal lesions present challenges to the clinician as far as diagnosis and prognosis of the involved teeth are concerned.Treatment and prognosis of endodontic–periodontal diseases vary and depend on the cause and the correct diagnosis of each specific condition. This book presents a review on pathogenesis of endo-perio lesions and their differential diagnosis. It also presents a study on role of non-surgical endodontic treatment as a sole treatment in management of endo-perio lesions. It also emphasizes on importance of long term follow-up in managing of such cases.