Nutrigenomics is the study of gene-nutrient interactions and how they affect the health and metabolism of an organism. Combining nutrigenomics with longevity studies is a natural extension and promises to help identify mechanisms whereby nutrients affect the aging process, life span, and, with the incorporation of age-dependent functional measures, health span. The topics we discuss in this chapter are genetic techniques, dietary manipulations, metabolic studies, and microarray analysis methods to investigate how nutrition affects gene expression, life span, triglyceride levels, total protein levels, and live weight in Drosophila. To better illustrate nutrigenomic techniques, we analyzed Drosophila larvae or adults fed control diets (high sucrose) and compared these with larvae or adults fed diets high in the saturated fat palmitic acid, soy, or 95% lean ground beef. The main results of these studies are, surprisingly, that triglyceride and total protein levels are significantly decreased by the beef diet in all adults, and total protein levels are significantly increased in male flies fed the soy diet. Furthermore, and less surprisingly, we found that all three experimental diets significantly decreased longevity and increased the length of time to develop from egg to adult. We also describe preliminary microarray results with adult flies fed the different diets, which suggest that only about 2-3% of the approx 18,000 genes have significantly altered mRNA expression levels compared with flies fed a control sucrose diet. The significance of these results and other types of nutrigenomics and longevity analyses is discussed. © Humana Press Inc.