The ability of an organism to sense and store nutrients is vital to survival. The liver is the major organ responsible for converting excess dietary carbohydrate to lipid for storage. An elegant molecular pathway has evolved that allows increased glucose flux into hepatocytes to generate a signaling molecule, xylulose 5-phosphate, that triggers rapid changes in glycolytic enzyme activities and nuclear import of a transcription factor, ChREBP, which coordinates the transcriptional regulation of enzymes that channel the glycolytic end-products into lipogenesis. Further understanding of this metabolic cascade should provide insights on conditions such as fatty liver, obesity, and the metabolic syndrome.