The relationship between the periodontium and pulp can be traced back to embryonical, anatomical, and functional origins. Dental papilla and follicle are products of the proliferation of ectomesenchymal cells. Clinicians need to recognize the importance of this communication and its consequences on disease development and later management. Therefore, in this paper, we will review the proper literature discussing the Periodontal – endodontic lesions. The literature search was carried out within the PubMed database using the keywords: “combined periodontal-endodontic lesion”, “periodontal treatment”, “root canal therapy”, “combined lesions” and “perio-endo lesion” from 1990 to 2021. Multiple etiologic factors have contributed to the development of Periodontal – endodontic lesions. Nevertheless, the concept of microbial involvement has been reputed as being the most likely culprit. Plaque that is formed by Bacteria on the denuded root surfaces, which occurs after periodontal disease induces different pathological malformations in the pulp which is facilitated by lateral or accessory canals. To conclude, doctors need to comprehend that endodontic therapy is rather foreseeable than the two diseases in periodontal–endodontic lesions. Nevertheless, the achievement of success of endodontic treatment is dependent on the fulfillment of periodontal treatment. The comprehensive therapy of both perspectives of periodontal – endodontic lesions is important for effective long-run outcomes.