A large and growing body of evidence indicates that dietary fatty acids regulate crucial metabolic processes involved in the pathogenesis of coronary heart disease (CHD). Despite this evidence, optimal dietary fatty acid intakes for CHD prevention remain unclear. Significant gaps in the modern nutrition literature and contradictions in its interpretation have precluded broad consensus. These shortcomings can be addressed through the incorporation of evolutionary, historical, and global perspectives. The objective of this review is to propose a unified theory of optimal dietary fatty acid intake for CHD prevention that integrates critical insights from evolutionary, historical, global, and modern perspectives. This broad approach may be more likely than previous methods to characterize optimal fatty acid intakes.