One of the most pressing challenges for the next 50 years is to reduce the impact of chronic disease. Unhealthy eating is an increasing problem and underlies much of the increase in mortality from chronic diseases that is occurring worldwide. Diets rich in plant-based foods are strongly associated with reduced risks of major chronic diseases, but the constituents in plants that promote health have proved difficult to identify with certainty. This, in turn, has confounded the precision of dietary recommendations. Plant biochemistry can make significant contributions to human health through the identification and measurement of the many metabolites in plant-based foods, particularly those known to promote health (phytonutrients). Plant genetics and metabolic engineering can be used to make foods that differ only in their content of specific phytonutrients. Such foods offer research tools that can provide significant insight into which metabolites promote health and how they work. Plant science can reduce some of the complexity of the diet-health relationship, and through building multidisciplinary interactions with researchers in nutrition and the pathology of chronic diseases, plant scientists can contribute novel insight into which foods reduce the risk of chronic disease and how these foods work to impact human health.