Dietary guidelines, especially those designed to prevent the diseases of dietary excess, are a relatively new phenomenon in the United States. National dietary guidelines have been promulgated based on scientific reasoning and indirect evidence. In general, weak evidentiary support has been accepted as adequate justification for these guidelines. This low standard of evidence is based on several misconceptions, most importantly the belief that such guidelines could not cause harm. Using guidelines against dietary fat as a case in point, an analysis is provided that suggests that harm indeed may have been caused by the widespread dissemination of and adherence to these guidelines, through their contribution to the current epidemic of obesity and overweight in the U.S. An explanation is provided of what may have gone wrong in the development of dietary guidelines, and an alternative and more rigorous standard is proposed for evidentiary support, including the recommendation that when adequate evidence is not available, the best option may be to issue no guideline.