Although guided tissue regeneration (GTR) procedures in periodontitis lesions and around endosseous dental implants represent exciting new therapeutic modalities in periodontics, these treatments can fail because of shortcomings in surgical techniques, restriction in the size and shape of the defect, anatomic features interfering with surgery, or infectious complications. Our studies show that optimal tissue regeneration cannot be expected for a nonbioabsorbable barrier membrane placed in a site infected by periodontopathic microorganisms. Our data also indicate that treatment failure is most frequent in patients who harbor high levels of periodontal pathogens and show evidence of severe periodontitis in numerous teeth. To decrease the risk of infection and to ensure proper healing, periodontal therapy should precede insertion of the barrier membrane for GTR. Recently, we have studied the effect of the pathogens on periodontal GTR and guided bone regeneration around dental implants and the results are reviewed in this article.