The application of genomic technologies to the analysis of wine strains of Saccharomyces cerevisiae has greatly enhanced our understanding of both native and laboratory strains of this important model eukaryote. Not only are differences in transcript, protein, and metabolite profiles being uncovered, but the heritable basis of these differences is also being elucidated. Although some challenges remain in the application of functional genomic technologies to commercial and native strains of S. cerevisiae, recent improvements, particularly in data analysis, have greatly extended the utility of these tools. Comparative analysis of laboratory and wine isolates is refining our understanding of the mechanisms of genome evolution. Genomic analysis of Saccharomyces in native environments is providing evidence of gene function to previously uncharacterized open reading frames and delineating the physiological parameters of ecological niche specialization and stress adaptation. The wealth of information being generated will soon be utilized to construct commercial stains with more desirable phenotypes, traits that will be designed to be genetically stable under commercial production conditions.