Iron is an essential micronutrient for both microbes and humans alike. For well over half a century we have known that this element, in particular, plays a pivotal role in health and disease and, most especially, in shaping host-pathogen interactions. Intracellular iron concentrations serve as a critical signal in regulating the expression not only of high-affinity iron acquisition systems in bacteria, but also of toxins and other noted virulence factors produced by some major human pathogens. While we now are aware of many strategies that the host has devised to sequester iron from invading microbes, there are as many if not more sophisticated mechanisms by which successful pathogens overcome nutritional immunity imposed by the host. This review discusses some of the essential components of iron sequestration and scavenging mechanisms of the host, as well as representative Gram-negative and Gram-positive pathogens, and highlights recent advances in the field. Last, we address how the iron acquisition strategies of pathogenic bacteria may be exploited for the development of novel prophylactics or antimicrobials.