The role of nutrition in health is a profoundly important example of interactions between genotype and environment. Interaction defines for all organisms the way in which a complex biological system, a cell, responds to any change in its environment. This applies to all cells, whether microbial or larger. The current “-omic” era (genomic, proteomics, transcriptomics, etc.) of biomedical research has already provided an overwhelming plethora of data regarding the sequence blueprint that defines many organisms (e.g., humans, mice, plants, insects, worms, yeast, and bacteria). The usefulness of much of these data resemble that of the periodic table to chemistry; we have in our hands a massed array of critical information that on its own provides little insight into the mechanisms of life or death. The challenge is clear: How is this information to be used to the best advantage? It is striking that the differences that define diversity of organisms are relatively minor in number in relation to their relevance. Thus, it must be the manner in which this information is expressed, often in response to the environment, which defines the nature of an organism or a human being. Much of our understanding of gene regulation has been derived from basic experiments in bacteria (Escherichia coli) or yeast (Saccharomyces cerevisiae). Furthermore, genome projects for the latter organism have been in use for over a decade (the first yeast chromosome was sequenced in 19921 and the genome completed in 19952). An appreciation and a basic understanding of the contribution of model systems are thus worthwhile. In this review we focus on the manner in which studies with a less complex eukaryote, yeast, have relevance to our interpretation of the human genome. We examine how yeast genetic approaches have increased our understanding of interactions between genotype and environment and in particular discuss how the handling of resources (i.e., nutrients) is achieved by this model eukaryote.