Diagnosis and management of periodontal-endodontic lesions are often complicated by the close interrelationship between periodontal tissues and dental pulps. Communications between both biological entities may occur through the apical foramen, accessory canals or exposed dentinal tubules, allowing bi-directional spread of infection and/or inflammation. Endodontic and periodontal lesions may occur distinctly or in tandem. Infected pulps may provoke an inflammatory response in adjoining periodontal tissues, and induce tissue destruction, and likewise, periodontal infection may elicit progressive pulpal pathoses. Solely periodontal or solely endodontic lesions are often clinically recognizable as distinct pathologies. However reported pain from pulpal or periodontal tissues may be similar, especially in combined lesions in which both endodontic and periodontal infection co-exist. When combined lesions develop, signs and symptoms such as toothache, tooth mobility, increased probing pocket depths and localized swelling may develop concurrently. As such, appropriate diagnostic tests and detailed clinical examination are required to differentiate periodontal, endodontic and combined pathologies and to arrive at correct diagnoses. Successful treatment outcomes for any periodontal and/or endodontic lesion depend on correct diagnosis and timely implementation of appropriate therapies. In this chapter, available evidence on periodontal-endodontic lesions will be reviewed with classification, clinical presentations, prognoses and treatment modalities discussed collectively.