Because glucose is the principal carbon and energy source for most cells, most organisms have evolved numerous and sophisticated mechanisms for sensing glucose and responding to it appropriately. This is especially apparent in the yeast Saccharomyces cerevisiae, where these regulatory mechanisms determine the distinctive fermentative metabolism of yeast, a lifestyle it shares with many kinds of tumour cells. Because energy generation by fermentation of glucose is inefficient, yeast cells must vigorously metabolize glucose. They do this, in part, by carefully regulating the first, rate-limiting step of glucose utilization: its transport. Yeast cells have learned how to sense the amount of glucose that is available and respond by expressing the most appropriate of its 17 glucose transporters. They do this through a signal transduction pathway that begins at the cell surface with the Snf3 and Rgt2 glucose sensors and ends in the nucleus with the Rgt1 transcription factor that regulates expression of genes encoding glucose transporters. We explain this glucose signal transduction pathway, and describe how it fits into a highly interconnected regulatory network of glucose sensing pathways that probably evolved to ensure rapid and sensitive response of the cell to changing levels of glucose.