The water-gas shift reaction has been investigated by using DFT applied to Au(100), stepped Au(310), and TiO2 anatase (001) surfaces. The results show that neither Au nor TiO2 can catalyze the reaction by themselves. Of CO, CO2, H2O, and H-2, only CO adsorbs with moderate adsorption energy at low-coordinated sites, whereas other molecules interact only weakly with Au. The activation of H2O is impossible on Au surfaces. However, H2O adsorbs dissociatively on the anatase (001) surface and the diffusion of OH and H is feasible. The energetic data indicate that the rest of the process is possible on the Au surface. Two mechanisms were investigated and compared for the water-gas shift reaction, with H2O dissociation on the TiO2 surface and diffusion of OH and H on Au surfaces in common. The latter is, in principle, the rate-limiting step. The first mechanism occurs through the disproportionation of two OH groups on Au into H2O and an O atom. The latter reacts with CO. In the alternative mechanism, CO combines with OH to give a COOH intermediate, which subsequently reacts with another OH group to form CO2 and H2O. Finally, H atoms recombine on the Au surface to complete the catalytic cycle.