Over the past two decades, prominent importance of molybdenum/tungsten-containing enzymes in prokaryotes has been put forward by studies originating from different fields providing a unique combination of knowledge. Proteomic or bioinformatic studies underpinned that the list of molybdenum/tungsten-containing enzymes is far from being complete with, to date, more than 50 different enzymes involved in the biogeochemical nitrogen, carbon and sulfur cycles. In particular, the vast majority of prokaryotic molybdenum-/tungsten-containing enzymes belong to the so-called DMSO reductase family. Despite its extraordinary diversity, this family is characterized by the presence of a Mo/W-bis(pyranopterin guanosine dinucleotide) cofactor at the active site with a yet uncovered reactivity. This chapter highlights the substrate specificity of their catalytic site, the modular variation of their structural organization and their contribution to the bioenergetics of prokaryotes.