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During past decades the relationship between dentistry and internal medicine and especially the concept of the so-called focal infection theory have long been a matter of debate. The pathogenesis of focal diseases has been classically attributed to dental pulp pathologies and periapical infections. Nonetheless, in recent years, their role is being dismissed while increasing interest is being devoted to the possible associations between periodontal infection and systemic diseases. In fact, periodontal pathogens and their products, as well as inflammatory mediators produced in periodontal tissues, might enter the bloodstream, causing systemic effects and/or contributing to systemic diseases. On the basis of this mechanism, chronic periodontitis has been suggested as a risk factor for cardiovascular diseases associated with atherosclerosis, bacterial endocarditis, diabetes mellitus, respiratory disease, preterm delivery, rheumatoid arthritis, and, recently, osteoporosis, pancreatic cancer, metabolic syndrome, renal diseases and neurodegenerative diseases such as Alzheimer's disease. Various hypotheses, including common susceptibility, systemic inflammation, direct bacterial infection and cross-reactivity, or molecular mimicry, between bacterial antigens and self-antigens, have been postulated to explain these relationships. In this scenario, the association of periodontal disease with systemic diseases has set the stage for introducing the concept of periodontal medicine. This narrative review summarizes the evolution of focal infection theory up to the current pathophysiology of periodontal disease, and presents an update on the relationships between chronic periodontitis and systemic diseases. more...