Single-atom catalysts (SACs) have attracted great attention in heterogeneous catalysis. In this Feature Article, we summarize the recent advances of typical Au and Pt-group-metal (PGM) based SACs and their applications in the water-gas shift (WGS) reaction in the past two decades. First, oxide and carbide supported single atoms are categorized. Then, the active sites in the WGS reaction are identified and discussed, with SACs as the positive state or metallic state. After that, the reaction mechanisms of the WGS are presented, which are classified into two categories of redox mechanism and associative mechanism. Finally, the challenges and opportunities in this emerging field for the collection of hydrogen are proposed on the basis of current developments. It is believed that more and more exciting findings based on SACs are forthcoming.