A new paradigm for the pathobiology of periodontitis is presented, and the manner in which periodontitis may relate to susceptibility for certain systemic diseases such as cardiovascular disease and preterm labor is described. Periodontitis is caused by a small group of Gram-negative bacteria present on the tooth root surfaces as bioffilms. Lipopolysaccharide (LPS) and other substances gain access to the gingival tissues, initiate and perpetuate immunoinflammation, resulting in production of high levels of proinflammatory cytokines. These induce production of matrix metalloproteinases which destroy the connective tissues of the gingiva and periodontal ligament, and prostaglandins which mediate alveolar bone destruction. Periodontitis may enhance susceptibility to systemic diseases in several ways. LPS and viable Gram-negative bacteria from the biofilms and proinflammatory cytokines from the inflamed periodontal tissues may enter the circulation in pathogenic quantities. In addition, periodontitis and certain systemic diseases, such as cardiovascular disease, share risk factors including tobacco smoking, male gender, race/ethnicity, stress, and aging.