Endodontic-periodontal lesions are a challenge to everyday clinical practice. The key factor to achieve success in treatment of endodontic periodontic lesions is elimination of the disease process in both areas. .In cases where there is combined lesion, the endodontic treatment helps in elimination of existing inflammation and healing of the endodontic component while the tooth survival and prognosis depends on healing of periodontal lesion. This article aims to discuss clinical, microbial, and the radiological aspects involved in diagnosis and sequential treatment protocol of perio-endo lesions.