Iron is essential for both host and pathogen, and complex systems of acquisition and utilization have evolved in competition. Our increasing knowledge of the basic mechanisms of homeostasis and their adaptation during deficiency, overload, and infection indicate that iron is a key regulator of host pathogen interactions. This review concentrated on the clinical and public health aspects of the interaction between the iron acquisition mechanisms of select pathogens of public health importance with host iron homeostasis. Knowledge of these interactions is essential in assessing likely morbidity responses to supplementation.