Plants, restricted by their environment, need to integrate a wide variety of stimuli with their metabolic activity, growth and development. Sugars, generated by photosynthetic carbon fixation, are central in coordinating metabolic fluxes in response to the changing environment and in providing cells and tissues with the necessary energy for continued growth and survival. A complex network of metabolic and hormone signaling pathways are intimately linked to diverse sugar responses. A combination of genetic, cellular and systems analyses have uncovered nuclear HXK1 (hexokinase1) as a pivotal and conserved glucose sensor, directly mediating transcription regulation, while the KIN10/11 energy sensor protein kinases function as master regulators of transcription networks under sugar and energy deprivation conditions. The involvement of disaccharide signals in the regulation of specific cellular processes and the potential role of cell surface receptors in mediating sugar signals add to the complexity. This chapter gives an overview of our current insight in the sugar sensing and signaling network and describes some of the molecular mechanisms involved.