Periodontitis is characterized by a chronic inflammation produced in response to a disease-associated multispecies bacterial community in the subgingival region. Although the inflammatory processes occur locally in the oral cavity, several studies have determined that inflammatory mediators produced during periodontitis, as well as subgingival species and bacterial components, can disseminate from the oral cavity, contributing therefore, to various extraoral diseases like systemic AA amyloidosis. Interestingly, amyloidosis associated with periodontal species has been observed in both the oral cavity and extra oral sites. A few studies were showing a strong association between amyloidosis and poor oral health, presence of periodontitis –associated bacteria, tooth loss and clinical signs of periodontitis. Proinflammatory pathways are activated either by mono-or polymicrobial infections, resulting in an increase in the expression of proinflammatory molecules such as IL-6,IL-8,IL-1? and TNF-?. In addition, it has been shown that several periodontitis –associated species induce the expression of genes related to cell proliferation, cell cycle, apoptosis, transport and immune and inflamatory responses. Intriguinly, many of these pathways are linked to systemic AA amyloidosis. Periodontitis can increase the levels of acute-phase reactans and potentiate the development of amyloidosis either by themselves or association with traditional factors, such as familial Mediterranean fever and other chronic inflammatory diseases. Thus, preventing or treating periodontitis might prevent or at least alleviate the progression of amyloidosis. Periodontal evaluation should be performed as part of a medical assessment and considered as an etiologic factor for secondary amyloidosis. It is hoped that medical, dental practitioners, and other health-care professionals will be familiar with perio-systemic link and risk factors, and need to refer to the specialized dental care.