Focal infection theory is the historical concept that many chronic diseases, including systemic and common ones, are caused by focal infections. In present medical consensus, a focal infection is a localised infection, often asymptomatic, that causes disease elsewhere in the host, but focal infections are fairly infrequent and limited to fairly uncommon diseases. (Distant injury is focal infection's key principle, whereas in ordinary infectious disease, the infection itself is systemic, as in measles, or the initially infected site is readily identifiable and invasion progresses contiguously, as in gangrene.) Focal infection theory, rather, so explained virtually all diseases, including arthritis, atherosclerosis, cancer, and mental illnesses.

An ancient concept that took modern form around 1900, focal infection theory was widely accepted in medicine by the 1920s. In the theory, the focus of infection might lead to secondary infections at sites particularly susceptible to such microbial species or toxin. Commonly alleged foci were diverse—appendix, urinary bladder, gall bladder, kidney, liver, prostate, and nasal sinuses—but most commonly were oral. Besides dental decay and infected tonsils, both dental restorations and especially endodontically treated teeth were blamed as foci. The putative oral sepsis was countered by tonsillectomies and tooth extractions, including of endodontically treated teeth and even of apparently healthy teeth, newly popular approaches—sometimes leaving individuals toothless—to treat or prevent diverse diseases.

Drawing severe criticism in the 1930s, focal infection theory—whose popularity zealously exceeded consensus evidence—was discredited in the 1940s by research attacks that drew overwhelming consensus of this sweeping theory's falsity. Thereupon, dental restorations and endodontic therapy became again favored. Untreated endodontic disease retained mainstream recognition as fostering systemic disease. But only alternative medicine and later biological dentistry continued highlighting sites of dental treatment—still endodontic therapy, but, more recently, also dental implant, and even tooth extraction, too—as foci of infection causing chronic and systemic diseases. In mainstream dentistry and medicine, the primary recognition of focal infection is endocarditis, if oral bacteria enter blood and infect the heart, perhaps its valves.

Entering the 21st century, scientific evidence supporting general relevance of focal infections remained slim, yet evolved understandings of disease mechanisms had established a third possible mechanism—altogether, metastasis of infection, metastatic toxic injury, and, as recently revealed, metastatic immunologic injury—that might occur simultaneously and even interact. Meanwhile, focal infection theory has gained renewed attention, as dental infections apparently are widespread and significant contributors to systemic diseases, although mainstream attention is on ordinary periodontal disease, not on hypotheses of stealth infections via dental treatment. Despite some doubts renewed in the 1990s by conventional dentistry's critics, dentistry scholars maintain that endodontic therapy can be performed without creating focal infections.