Herein we give an account of our work on catalyst design for the low-temperature water-gas shift (WGS) reaction. The reaction is catalyzed by single-site, oxygen coordinated metal cations on various supports. Using two different metals, namely Au and Pt, we have found that the two metals form similarly-structured active sites, comprising isolated metal cations, coordinated with several -O bonds to a metal oxide that serves as the support of the active gold or platinum species. The support can be a reducible oxide, e.g. CeO2, FeOx, TiO2, a non-reducible oxide, e.g. silica, zeolites, alumina, or even a non-oxide support, like carbon nanotubes. In the latter cases, alkali (Na, K)-Ox-linkages are used as a first shell around the metal ion center, stabilizing it, and supplying the -OH species necessary for the reaction. The turnover rates per catalytic site are similar on any support, specific only to the nature of the metal cation of the active site: Au(I) or Pt(II). Accordingly, the apparent activation energy, E-app, is different for each metal; 45 +/- 5 kJ/mol for gold, and 70 +/- 10 kJ/mol for the platinum catalysts. The evolution of preparation methods from those involving mixed metal structures (nanoparticles, clusters, and atoms) to novel ones that give exclusively single-atom metal catalytic centers on a support is discussed. The latter materials may be used as a platform to check whether a reaction occurs via single-atom catalytic centers. The findings are general and can be easily extended to other oxygen-coordinated metal ions on supports for the WGS reaction. They may also find broader applications to different reactions in fuel conversion and green chemicals production.