The complex processes of the cell depend upon differential expression of sets of genes either in particular cell types, at different times, or under certain environmental conditions. Thus within cells there are programs whereby sets of genes are coordinately switched on or off. In yeast the GAL genes encode the enzymes required for normal galactose metabolism. Regulation of these genes in response to the organism being challenged with galactose has served as a paradigm for eukaryotic transcriptional control over the last 50 years. Three proteins - the activator Gal4p, the repressor Gal80p, and the ligand sensor Gal3p - control the switch between inert and active gene expression. Gal80p, the focus of our recent structural studies, plays a pivotal role both in terms of repressing the activity of Gal4p and allowing the GAL switch to respond to galactose.