Transition metals such as manganese are essential nutrients for both pathogen and host. Vertebrates exploit this necessity to combat invading microbes by restricting access to these critical nutrients, a defense known as nutritional immunity. During infection, the host uses several mechanisms to impose manganese limitation. These include removal of manganese from the phagolysosome, sequestration of extracellular manganese, and utilization of other metals to prevent bacterial acquisition of manganese. In order to cause disease, pathogens employ a variety of mechanisms that enable them to adapt to and counter nutritional immunity. These adaptations include, but are likely not limited to, manganese-sensing regulators and high-affinity manganese transporters. Even though successful pathogens can overcome host-imposed manganese starvation, this defense inhibits manganese-dependent processes, reducing the ability of these microbes to cause disease. While the full impact of host-imposed manganese starvation on bacteria is unknown, critical bacterial virulence factors such as superoxide dismutases are inhibited. This chapter will review the factors involved in the competition for manganese at the host–pathogen interface and discuss the impact that limiting the availability of this metal has on invading bacteria.