Two patients were diagnosed with combined endodontic-periodontal lesions. Endodontic treatment was performed, followed by surgery. In addition, the regeneration process was supported by the application of an enamel matrix derivate alone or in combination with guided bone regeneration techniques. At recall visits after 24 months, the teeth were asymptomatic and marked bone regeneration had occurred in both patients. The successful post-endodontic treatment of combined endodontic-periodontal lesions, using periodontal surgery and as adjunct guided tissue regenerative techniques, is presented. Further, the possibility of saving teeth, even with severely apparent pathology, should be highlighted.