The ability of microorganisms that would like to live in or on mammalian hosts to acquire iron is a critical determinant of the host-parasite interaction. Despite the abundance of iron, its availability to microbes is restricted by the iron-binding and transport systems of the host. The successful commensal or pathogen therefore must express effective systems to compete for its iron. The acquisition of iron is thus essential, although not sufficient, for virulence. This review examines host and microbial iron-acquisition and transport mechanisms in an attempt to stimulate the reader's interest in potential "soft spots" that may be exploited prophylactically and therapeutically.