Research with budding yeast (Saccharomyces cerevisiae) has been transformed by the publication, nearly a decade ago, of the entire genome DNA sequence. The introduction of this first eukaryotic genomic sequence changed the yeast research environment significantly, not just because of dramatic progress in technical means but also because the sequence made accessible a new class of scientific questions. A central goal of yeast research remains the determination of the biological role of every sequence feature in the yeast genome. The most remarkable change has been the shift in perspective from focus on individual genes and functionalities to a more global view of how the cellular networks and systems interact and function together to produce the highly evolved organism we see today.