During the twentieth century, plant breeding and genetics improved the nutritive value of horticultural and agronomic crops, particularly of macro-nutrients and fiber. Current research focuses more on micronutrients. Successful development of phytonutrient-enriched crop plants will be bolstered by interdisciplinary collaborative research, analytical and biotechnology advances, and public education. Although the melding of plant and nutrition research holds great promise, the genetic enhancement of crop plants for improved phytonutrient content will be challenging. This paper reviews the knowledge base on which genetic enhancement may be based, identifies gaps in scientific knowledge and technical capacities, and suggests a role for the federal government in research.