While large populations in the third world are enduring famine, much of the developed world is undergoing an obesity epidemic. In addition to reflecting an unbalanced distribution of food, the “epidemic of overabundance” is ironically leading to a decrease in the health and longevity of the obese and improperly nourished in the first world. International consortia, such as the European Nutrigenomics Organization (NuGO), are increasing our knowledge of nutrientgene interactions and the effects of diet and obesity on human health. In this review, we summarize both previous and ongoing nutrigenomics studies in Drosophila and we explain how these studies can be used to provide insights into molecular mechanisms underlying nutrigenomics in humans. We will discuss how quantitative trait locus (QTL) experiments have identified genes that affect triglyceride levels in Drosophila, and how microarray analyses show that hundreds of genes have altered gene expression under different dietary conditions. Finally, we will discuss ongoing combined microarray-QTL studies, termed “genetical genomics,” that promise to identify “master modulatory loci” that regulate global responses of potentially hundreds of genes under different dietary conditions. When “master modulatory loci” are identified in Drosophila, then experiments in mammalian models can be used to determine the relevance of these genes to human nutrition and health.