AbstractSeveral dietary approaches have been proposed to prevent the onset of chronic diseases. As yet, no single approach has emerged as having the most consistent health benefits. This arises, in part, due to the fact that diet influences health in the context of individual factors with genetic components. Therefore, the effects of diet on health may be dependent on an individual’s genetic background. At this time we lack robust evidence for the effects of interactions between genes and dietary patterns on health. To understand why, I will briefly review the most methodologically strong attempts to identify gene–diet interactions, which will illuminate how the challenges facing all of genetic research apply to the search for gene–diet interactions. Then I will discuss some ways in which these challenges are being addressed that offer hope for the future in which the best diet for an individual is identified based on their genetic variation.