Iron holds a central position at the host–pathogen interface because mammalian and microbial cells have an essential demand for the metal, which is required for many metabolic processes. In addition, cross-regulatory interactions between iron homeostasis and immune function are evident. While iron affects the secretion of cytokines and the activity of transcription factors orchestrating immune responses, immune cell-derived mediators and acute-phase proteins control both systemic and cellular iron homeostasis. Additionally, immune-mediated strategies aim at restricting the supply of the essential nutrient iron to pathogens, which represents an effective strategy of host defence. On the other hand, microbes have evoked multiple strategies to utilize iron because a sufficient supply of this metal is linked to pathogen proliferation, virulence and persistence. The control over iron homeostasis is a central battlefield in host–pathogen interplay influencing the course of an infectious disease in favour of either the mammalian host or the pathogenic invader. This review summarizes our current knowledge on the combat of host cells and pathogens for the essential nutrient iron focusing on the immune-regulatory roles of iron on cell-mediated immunity necessary to control intracellular microbes, the host's mechanisms of iron restriction and on the counter-acting iron-acquisition strategies employed by intracellular microbes.