The earliest forms of life (i.e., Archaea, Bacteria, and Eukarya) appeared on our planet about ten billion years after its formation. Although Archaea do not seem to possess the multiprotein machinery constituted by the NIF (Nitrogen Fixation), ISC (Iron Sulfur Cluster), SUF (sulfur mobilization) enzymes, typical of Bacteria and Eukarya, some of them are able to encode Fe-S proteins. Here we discussed the multiple enzymatic reactions triggered by the up-to-date structurally characterized members of the archaeal family that require the crucial presence of structurally characterized [2Fe-2S] assemblies, focusing on their biological functions and, when available, on their electrochemical behavior.