Periodontal disease, or periodontitis, is a globally widespread pathology of the human oral cavity. Indeed, approximately 10% of the global adult population is highly vulnerable to severe periodontitis. Another 10–15% appears to be completely resistant to it, while the remainder vary between these two extremes . Moreover, the prevalence of periodontitis is peaking at the fourth decade of life and increasing to 70–85% in the age group of 60–65 . Strikingly, despite major improvements in oral hygiene practices today, these proportions are not far from what was reported in possibly the frst epidemiological report of periodontitis in humans back in 1918 (then defned as periodontoclasia or pyorrhea alveolaris). According to that, the prevalence of the disease in the Chicago area was 13% in the age range of 20–24, 68% in 30–39, and 88% over 50. Much recent data from USA showed that there is not a drop but rather an increase in these numbers among the older individuals . That means that periodontitis is an inevitable oral pathology of the human population, and its prevalence increases with age. Taking also underconsideration the increasing life expectancy, periodontitis is a growing health problem. Despite the persistence of severe periodontitis even in the twenty-frst century, the last 100 years have witnessed a signifcant progress in our understanding of its pathogenesis, that is, the conglomerate of biological processes that lead to the disease. Nevertheless, the actual “coordinator(s) ”of the disease is still an issue of intense debate. Microbiology researchers place emphasis in seeking species, or combinations of them, associated with different clinical forms of the disease. On the other side, immunologists are in pursuit of cells and molecules that orchestrate the tissue-destructive inflammation, as a result of the bacterial challenge.