Severe loss of peri-implant supporting bone traditionally leads to the removal of the affected implant, but this may not be necessary in all cases. This paper presents a novel treatment approach aimed at the successful regeneration of bone lost to peri-implantitis using guided tissue regeneration (GTR). Four years after implant placement two patients presented with severe peri-implant tissue breakdown. Clinical signs of disease included bleeding on probing, suppuration, increased probeable pocket depth (4 to 9 mm) and a decreased level of clinical attachment (2 to 10 mm). Radiographic analysis revealed 2.6 to 7.1 mm loss of supporting bone. Treatment of these lesions included raising flaps, wound debridement, and rinsing with sterile saline and 0.2% chlorhexidine digluconate. Subsequently, ePTFE membranes were adapted around the necks of the implants and the flaps sutured around the necks of the implants, allowing for transmucosal healing. Both patients were placed on a 10-day antibiotic regimen and instructed to rinse twice daily with a 0.12% chlorhexidine solution. They were reevaluated every 3 weeks at which time professional plaque control was performed. After 4 1/2 and 6 1/2 months, respectively, the membranes required removal due to infection. The radiographic analysis 1 year after membrane removal revealed 1.5 to 3.6 mm of bone gain. As a result of regenerative therapy the implants in both these patients were successfully maintained. It can be concluded that implants with severe loss of bone resulting from peri-implantitis need not always be extracted. A potential approach for the treatment of peri-implant bone destruction is GTR therapy using strict attention to good antimicrobial therapy.