Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron content is an important step towards a better public health. Our review focuses on the control of iron acquisition in dicotyledonous plants and monocots that apply a reduction-based strategy in order to mobilize and import iron from the rhizosphere. Achieving a balance between shortage and excess of iron requires a tight regulation of the activity of the iron uptake system. A number of studies, ranging from single gene characterization to systems biology analyses, have led to the rapid expansion of our knowledge on iron uptake in recent years. Here, we summarize the novel insights into the regulation of iron acquisition and internal mobilization from intracellular stores. We present a detailed view of the main known regulatory networks defined by the Arabidopsis regulators FIT and POPEYE (PYE). Additionally, we analyze the root and leaf iron-responsive regulatory networks, revealing novel potential gene interactions and reliable iron-deficiency marker genes. We discuss perspectives and open questions with regard to iron sensing and post-translational regulation.