Periodontal diseases, some of the most common infectious diseases seen in humans, are characterized by gingival inflammation, as well as loss of connective tissue and bone from around the roots of the teeth, which leads to eventual tooth exfoliation. In the past decade, the association of periodontal diseases with the development of systemic diseases has received increasing attention. Although a number of studies have presented evidence of close relationships between periodontal and systemic diseases, the majority of findings are limited to epidemiological studies, while the etiological details remain unclear. Nevertheless, a variety of recent hypothesis driven investigations have compiled various results showing that periodontal infection and subsequent direct oral-hematogenous spread of bacteria are implicated in the development of various systemic diseases. Herein, we present current understanding in regard to the relationship between periodontal and systemic diseases, including cardiovascular diseases, preterm delivery of low birth weight, diabetes mellitus, respiratory diseases, and osteoporosis.