A healthy periodontium is vital for the general well-being of an individual. However, periodontal diseases are common and periodontal infections are increasingly associated with systemic diseases. We aimed to critically evaluate the literature on the association between periodontal infections and systemic diseases. We searched the PubMed database over a 20-year period for literature on periodontal diseases and their links to various systemic diseases, and examined the strength of association between periodontal disease and each systemic disease, the dose-response relationship, and the biological plausibility. We found that individuals with periodontal disease may be at higher risk for adverse medical outcomes including cardiovascular diseases, respiratory infections, adverse pregnancy outcomes, rheumatoid arthritis and diabetes mellitus. Many cohort, in vitro and animal studies suggest that systemic inflammation due to pathogens associated with periodontal disease may play a role in the initiation and progression of some systemic diseases. Periodontal infections should therefore be considered as a risk factor for various systemic diseases.