Our understanding of infectious diseases continues to expand rapidly, and has led to the realization that microorganisms are responsible for, or at least contribute to, numerous diseases that were never before associated with infectious etiologies. However, a review of medical history reminds us that this is not so novel an idea. Not long after the widespread acceptance of bacteriology and the germ theory and with an increased awareness of public hygiene, there was a period during which it seemed that nearly all diseases would prove to be the result of infections. One popular proposal that championed such an idea was the theory of focal infection. This article reviews this theory by considering the key concepts and developments that likely inspired it, and examines the work of the theory's most visible proponent, Dr. Frank Billings.