Infection involves the utilization of host nutritional resources by the pathogen. Genetic, experimental, and clinical evidence supports the critical role of iron as a focus for both pathogen attack and host defense. The molecular basis of how mammals regulate iron transport to maintain homeostasis, and in response to infection, has been well characterized since the discovery of the hormone hepcidin. The multiple activities of iron in host innate and adaptive immune cell function have also been studied in increasing depth. Recently these research strands have been converging, showing how host regulation of iron affects not only classical "nutritional immunity" as a defense against pathogens but also influences the development and magnitude of immune responses. These findings are discussed in the context of different types of infectious micro-organisms, against a background of host disease states (including respiratory disorders), and in relation to iron supplementation, vaccination, and pathological immune responses.