| Summary: | Sulfur is not only one of the most abundant elements on the Earth, but it is also essential to all living organisms. As life likely began and evolved in a hydrogen sulfide (H<sub>2</sub>S)-rich environment, sulfur metabolism represents an early form of energy generation via various reactions in prokaryotes and has driven the sulfur biogeochemical cycle since. It has long been known that H<sub>2</sub>S is toxic to cells at high concentrations, but now this gaseous molecule, at the physiological level, is recognized as a signaling molecule and a regulator of critical biological processes. Recently, many metabolites of H<sub>2</sub>S, collectively called reactive sulfur species (RSS), have been gradually appreciated as having similar or divergent regulatory roles compared with H<sub>2</sub>S in living organisms, especially mammals. In prokaryotes, even in bacteria, investigations into generation and physiology of RSS remain preliminary and an understanding of the relevant biological processes is still in its infancy. Despite this, recent and exciting advances in the fields are many. Here, we discuss abiotic and biotic generation of H<sub>2</sub>S/RSS, sulfur-transforming enzymes and their functioning mechanisms, and their physiological roles as well as the sensing and regulation of H<sub>2</sub>S/RSS.
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