Iron is an essential nutrient for all eukaryotic cells, yet it is potentially toxic. Cells have elegant systems coordinating the uptake, use, storage, and export of this metal while also responding to extracellular cues for regulating uptake and efflux. Here we describe the basic systems that operate in all cells with the goal of maintaining iron homeostasis in a highly dynamic system. In mammalian tissues and organs, multiple cell types are highly specialized in their iron management with the goal of maintaining cellular homeostasis subordinate to achieving a more specific function, e.g., dietary iron absorption in the intestinal epithelium, hemoglobin synthesis in the erythron, and iron recycling in splenic macrophages. The alterations in cellular iron balance that allow for these specializations will be briefly discussed.