Two areas of research have recently converged to highlight important roles for Mn2+ in pathogenesis: the recognition that both bacterial Nramp homologs and members of LraI family of proteins are Mn2+ transporters. Their mutation is associated with decreased virulence of various bacterial species. Thus, Mn2+ appears to be essential for bacterial virulence. This review describes what is currently known about Mn2+ transport in prokaryotes and how prokaryotic Mn2+ transport is regulated. Some of the phenotypes that arise when microorganisms lack Mn2+ are then discussed, with an emphasis on those phenotypes involving pathogenesis. The concluding section describes possible enzymatic roles for Mn2+ that might help explain why Mn2+ is necessary for virulence.