Most hydrogenases (H₂ases), the enzymes that produce or oxidize dihydrogen, possess dimetallic active sites and belong to either one of two phylogenetically distinct classes, the NiFe and the FeFe H₂ases. These families of H₂ases share a number of similarities regarding active site structure and reaction mechanism, as a result of convergent evolution. They are otherwise alien to each other, in particular with respect to protein sequence and structure, maturation mechanisms, and distribution among the realms of life. One of the interesting features of FeFe H₂ases is their occurrence in anaerobic bacteria, anaerobic protists, and mitochondriate eukaryotes. They thus have the potential to report on important evolutionary events, including transitions from the prokaryote to the eukaryote lifestyle. Genome sequences yield a variety of FeFe H₂ase sequences that have been implemented to shed light on the evolution of these proteins and their host organisms.