In recent years, the controversial focal infection theory (originally presented in the early 1900s) has received a resurgence of support, as oral infections have been linked to several systemic conditions. This article reviews pertinent literature detailing both the historical basis of the focal infection theory and current viewpoints on the possible association between oral and systemic diseases. Dental professionals should be aware of the potential negative effects of oral infections on systemic health. While endodontically treated teeth have not been implicated in systemic disease, effective treatment regimens for periodontal disease may reduce the occurrence of systemic disease for certain individuals.