Life's processes absolutely require inorganic phosphate for structural and energetic purposes. Escherichia coli has developed sophisticated mechanisms to acquire phosphate and to maintain intracellular amounts at optimal levels. The processes by which these simple cells maintain stable intracellular concentrations of phosphate are termed phosphate homeostasis, which involves mechanisms to balance the import, assimilation, sequestration, and export of phosphate. This chapter introduces the proteins involved in phosphate homeostasis and reviews information concerning the multiple phosphate transporters and the mechanisms by which they are regulated. It also introduces new concepts of how this bacterium responds to elevated extracellular levels of phosphate and presents a model for the integration of all of these processes to achieve homeostasis. The predominant importers are PitA, PitB, and the PstSCAB complex. Assimilation, or the incorporation of Pi into organic molecules, occurs primarily through the formation of ATP. Gene regulation relies on the PhoB/PhoR two-component system and the formation of a signaling complex at the membrane. The amount of intracellular phosphate can be fine-tuned through the formation or degradation of polyphosphate. Polyphosphate formation requires adequate supplies of ATP. In addition, when intracellular phosphate levels become too high, phosphate can be exported through PitA, PitB, or the YjbB transporters.