Two contradictory hypotheses on the role of dietary carbohydrates in health and disease shape how dental-systemic associations are regarded. On one side, Cleave and Yudkin postulated that excessive dietary fermentable carbohydrate intake led-in the absence of dental interventions such as fluorides-first to dental diseases and then to systemic diseases. Under this hypothesis, dental and systemic diseases shared-as a common cause-a diet of excess fermentable carbohydrates. Dental diseases were regarded as an alarm bell for future systemic diseases, and restricting carbohydrate intake prevented both dental and systemic diseases. On the opposite side, Keys postulated the lipid hypothesis: that excessive dietary lipid intake caused systemic diseases. Keys advocated a diet high in fermentable carbohydrate for the benefit of general health, and dental diseases became regarded as local dietary side effects. Because general health takes precedence over dental health when it comes to dietary recommendations, dental diseases became viewed as local infections; interventions such as fluorides, sealants, oral hygiene, antimicrobials, and dental fillings became synonymous with maintaining dental health, and carbohydrates were no longer considered as a common cause for dental-systemic diseases. These opposing dietary hypotheses have increasingly been put to the test in clinical trials. The emerging trial results favor Cleave-Yudkin's hypothesis and may affect preventive approaches for dental and systemic diseases.