Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth associated with a polymicrobial biofilm (subgingival plaque) accreted to the tooth which results in destruction of the tooth’s supporting tissues. A characteristic feature of the disease-associated plaque is the emergence of proteolytic species. One of these species, Porphyromonas gingivalis has recently been described as a keystone pathogen as it dysregulates the host immune response to favour the polymicrobial biofilm disrupting homeostasis to cause dysbiosis and disease.  The level of P. gingivalis in subgingival plaque above threshold levels (~10% of total bacterial cell load) has been demonstrated to predict imminent clinical attachment loss (disease progression) in humans. P. gingivalis is found as microcolonies in the superficial layers of subgingival plaque adjacent to the periodontal pocket epithelium which helps explain the strong association with underlying tissue inflammation and disease at relatively low proportions (10%) of the total bacterial cell load of the plaque. The mouse periodontitis model has been used to show that inflammation is essential to allow establishment of P. gingivalis at the levels in plaque (10% or greater of total bacterial cell load) necessary to produce dysbiosis and disease. The extracellular proteinases “gingipains” (RgpA/B and Kgp) of P. gingivalis have been implicated as major virulence factors that are critical for dysbiosis and disease. P. gingivalis and Treponema denticola are frequently found to co-exist in the pathogenic polymicrobial biofilm of deep periodontal pockets and have been co-localized to the superficial layer of subgingival plaque, suggesting interbacterial interactions.  When co-inoculated intra-orally in animal models of periodontitis P. gingivalis and T. denticola exhibit a synergistic pathogenesis.  The two species display a symbiotic relationship in nutrient utilization, growth promotion, motility and virulence which explains their intimate association.