Bacteria, archaca, unicellular eukaryotes, and plants have confronted fluoride ion in their environment over evolutionary time, and possess multiple lines of defense against this toxin that inhibits glycolytic enolase, pyrophosphatase, and other phosphoryl transfer enzymes. One such defense mechanism is the presence of membrane transport proteins to rid the cytoplasm of fluoride ions. Widespread microorganisms possess either of two classes of transporters from unrelated protein families: Fluc family of fluoride channels or the CLCF-type F-/H+ transporters. This talk will address the highly unusual structural and functions features of membrane transport proteins, using membrane protein biochemistry, electrophysiology and x-ray crystallography.