Herpesviruses appear to assume a major etiopathogenic role in various types of destructive periodontal disease. Human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and HCMV-EBV co-infection are closely associated with disease-active periodontitis in juveniles and adults, with acute necrotizing ulcerative gingivitis in children, and with periodontal abscesses. In particular, HCMV reactivation in periodontitis lesions seems to be linked to advancing disease. HCMV infects periodontal monocytes/macrophages and T-lymphocytes, and EBV infects periodontal B-lymphocytes. Herpesvirus-infected inflammatory cells generate a great variety of pro-inflammatory cytokines and may possess diminished ability to defend against bacterial challenge. Herpesvirus-associated periodontal sites tend to harbor elevated levels of periodontopathic bacteria, including Dialister pneumosintes, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Prevotella nigrescens, Treponema denticola, Campylobacter rectus and Actinobacillus actinomycetemcomitans. In summary, the available data suggest that periodontitis occurs more frequently and progresses more rapidly in herpesvirus-infected than in non-infected periodontal sites. An infectious disease model based on herpesvirus-bacteria-host immune response interactions is presented to explain how a gingivitis lesion or a stable periodontal site with increased probing depth may convert into a tissue-destroying periodontitis lesion.