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Diagnosis and management of endo-perio lesions differ from those lesions of single causative factor. These present signs and symptoms, which cannot be easily attributed or accounted for, require more detailed examination and definitive treatment plan. The outcomes are not readily predictable as of lesions of single origin. Distinguishing the primary etiological factor and overlapping secondary clinical features require thorough knowledge and understanding of the pathology, anatomy, and microbiology with respect to the teeth involved. The primary and secondary etiological factors can have numerous variations and hence makes arriving at a definitive treatment plan complex. However systematic examination combined with relevant investigations always provides a correct direction toward optimum treatment plan. This article presents four cases of endo-perio lesions and their successful management by different treatment modalities.