Geobacter species are often the predominant Fe(III)-reducing microorganisms in many sedimentary environments due to their capacity for extracellular electron transfer. This exceptional physiological capability allows them to couple acetate oxidation to uranium (U(VI)) reduction, that is one of the most significant interactions between radionuclides and microorganisms that naturally takes place in uranium-contaminated environments. Although this process has been proposed as a promising strategy for the in situ bioremediation of uranium-contaminated groundwater, little is known about the molecular mechanisms involved in U(VI) reduction and the interaction between Geobacter and other microbial species. In the first two research chapters, this dissertation aim to study the interaction between Geobacter sulfurreducens, a primary model organism to elucidate the physiological capabilities of Geobacter species, and U(VI). Our findings presented here suggest that G. sulfurreducens requires outer-surface c-type cytochromes, but not pili, for the reduction of uranium, and U(IV), the product of U(VI) reduction was precipitated at the outer cell surface. Our results also suggest that there is not one specific U(VI)-detoxification specific mechanism for uranium detoxification in G. sulfurreducens. Rather, resistance to U(VI) appears to be accomplished with multiple stress response systems, that includes detoxification and oxidative stress response, and regulatory networks that facilitate fast adaptation to rapidly changing conditions. The third research chapter of this dissertation examines the physiology of Desulfobacter postgatei, a competitor for acetate during in situ bioremediation of subsurface systems at a uranium-contaminated site in Rifle, CO. Our findings suggest that novel enzymatic complexes, such as the energy-converting hydrogenase related complex, Ehr, the proton-translocating ferredoxin:NADP+ oxidoreductase, Rnf, and also the NADH-dependent reduced ferredoxin:NADP+ oxidoreductase, Nfn, are involved in energy conservation, making D. postgatei a major competitor for acetate in several environments.