Periodontitis has been independently associated with several chronic diseases, including diabetes and heart disease. Current evidence supports three mechanisms that may explain periodontitis impact on other diseases. Those include shared risk factors, elevated systemic inflammation, and direct action of periodontal bacteria on distant organs. Recent analyses of insurance claims data indicate that treatment of periodontitis lead to lower medical costs in subsequent years. Small prospective periodontitis treatment studies were promising relative to improving certain medical conditions, but larger studies have not been supportive. Current evidence suggests that not all periodontitis patients are equal in effect on chronic diseases, and endpoints of periodontal therapy may need higher standards for a systemic effect. This presentation will discuss two paths relative to onset and progression of major chronic diseases and factors that contribute to which individuals are on the more aggressive path. Approaches for targeting certain periodontitis patients for more intensive therapy and monitoring will be discussed with a focus on prevention and improvement of certain chronic diseases.