Periodontal regeneration in patients with advanced periodontitis and severe attachment loss has classically presented some of the greatest challenges to the practitioner. The purpose of this article is to describe the staged treatment approach and long-term follow-up of a case with generalized advanced chronic periodontitis. Microbial sampling for suspected periodontopathogens was done before and after treatment. Autogenous bone grafting was used to repair bilateral mandibular vertical defects on both molars and premolars. Reentry surgery at 6 months demonstrated 100% defect fill. Clinical, radiographic, and microbiologic evidence at 8 years suggested a stable outcome. Qualitative polymerase chain reaction (PCR) analysis was done to detect the presence of cytomegalovirus, Epstein-Barr virus type 1, and common periodontopathogens 8 years after active periodontal therapy. Negative PCR results 8 years after treatment confirmed that pathogenic subgingival reservoirs were successfully eradicated.