By definition, functional foods benefit human health beyond the effect of nutrients alone. However, few are accompanied by convincing health claims, partly because human responses are variable. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients, such as n-3 polyunsaturated fatty acids, would affect the efficacy of that nutrient. However, functional foods often incorporate bioactive compounds, such as epigallocatechin-3-gallate, without considering the interaction with genetic polymorphisms. For either example there will be individuals whose genotype precludes their deriving significant benefit from an increased intake of such foods, and a small segment of the population that may be disadvantaged. Large-scale, whole-genome association studies are providing unprecedented understanding of the genetic basis of health and chronic disease. This rapidly evolving genomic science often fails to consider the interaction with environmental exposure like diet. It is important that the dietetics profession ensures rigorous nutrition science alongside genetic evaluation as part of future study design to derive informed information on gene-diet interactions that may enable clients to rationally select foods leading to optimal health or reduced risk of chronic disease.