Glucose has essential metabolic roles as both a fuel for energy and a substrate for the biosynthesis of cell components. Because of its central importance, many cells have evolved mechanisms to sense glucose levels in their environment and to adapt the expression of their genetic information to glucose availability. This glucose signaling is vital in mammalian cells where derangements in glucose utilization might contribute to conditions such as obesity and type 2 diabetes. Two crucial issues stand out in understanding pathways of glucose-regulated gene transcription. First, how do cells sense changing glucose levels? Second, how is this signal transduced to the transcriptional apparatus of the cell? In mammalian cells, glucose sensing involves the detection of changes in glucose metabolism rather than glucose itself. A transcription factor that is involved in mediating responses to glucose, ChREBP, has been identified recently and studies have begun to elucidate the molecular basis of coupling between glucose metabolism and transcription factor activity.