There is an increasing evidence that nutritional genomics represents a promise to improve public health. This goal will be reached by highlighting the mechanisms through which diet can reducethe risk of common polygenic diseases. Nutritional genomics applies high throughput functional genomic technologies and molecular tools in nutrition research, allowing a more precise and accurate knowledge of nutrient-genome interactions in both health and disease. Understanding the inter-relationships among genes, genes products, and dietary habits is fundamental to identify those who will benefit themost or be placed at risk by nutritional interventions. This chapter provides an overview of this novel nutritional approach, including themost relevant results of our recent research on the nutrigenomic effects of food polyphenols on cancer cells. Those studies would highlight themolecular mechanisms underlying the chemopreventive effects of those bioactive food compounds.