Iron deficiency is usually considered as an adverse condition which entails several unpleasant symptoms. Yet, restricted blood iron levels also constrain the proliferation of infectious agents. Therefore it is hypothesized that moderate iron deficiency may constitute an evolutionary adaption to invading pathogens. To evaluate this hypothesis, evidence for the molecular evolution of mechanisms of iron restriction in the human body and microbial mechanisms of iron acquisition is reviewed, as well as evidence documenting the beneficial impact of low blood iron levels in the presence of infectious agents. It is concluded that mechanisms to restrict iron levels during infection may in fact constitute an evolutionary adaption that has coevolved with bacterial mechanisms of iron acquisition and implications of this for healthcare are discussed.