Oxygen-resistant carbon monoxide dehydrogenases (CODHs) fall into two categories: those derived from aerobic CO-metabolizing bacteria and the engineered oxygen-resistant variants from anaerobic CO-metabolizing bacteria. The former, containing molybdenum (Mo) and copper (Cu) cofactors, are termed as Mo/Cu-CODHs. They specifically catalyze the oxidation of carbon monoxide (CO) to carbon dioxide (CO2), generating two protons (H+) and two electrons (e-) in the process, and are insensitive to O2. The latter, Ni/Fe-CODHs, featuring nickel (Ni) and iron (Fe) cofactors, originate from anaerobic CO-metabolizing bacteria. Most Ni/Fe-CODHs are O2-sensitive, though some variants exhibit limited O2 tolerance at the expense of reduced activity. Nevertheless, high-activity Ni/Fe-CODHs can be engineered for oxygen tolerance. Unaffected by O2 concentration, oxygen-tolerant CODHs hold significant application potential in biomanufacturing and electrochemistry under aerobic conditions. This work first reviews the structure, function, and catalytic mechanisms of Mo/Cu-CODHs. Mo/Cu-CODHs comprise three subunits (coxL, coxS, coxM), with CO oxidation primarily occurring at the active site of the L subunit. The catalytic mechanism of CO oxidation by this enzyme has been largely elucidated: CO initially binds to Cu, followed by nucleophilic attack by the O ligand of Mo=O to form five-membered ring intermediates. A sequence of subsequent intermediates, including thiocyclic carbonate, then ensues, ultimately leading to CO2 release and completion of the catalytic cycle. Additionally, this work explores the factors influencing the oxygen tolerance of Ni/Fe-CODHs and methods to enhance this trait. It also summarizes progress in the in vitro heterologous expression and purification of oxygen-tolerant CODHs, reviews their applications in the bioconversion of synthetic chemicals and in vitro catalysis, and provides an outlook on future development trends. These contents will offer references for further research and development of oxygen-tolerant CODHs.