Sulfide and transition metals often came together in Biology. The variety of possible structural combinations enabled living organisms to evolve an array of highly versatile metal-sulfide centers to fulfill different physiological roles. The ubiquitous iron‑sulfur centers, with their structural, redox, and functional diversity, are certainly the best-known partners, but other metal-sulfide centers, involving copper, nickel, molybdenum or tungsten, are equally crucial for Life. This review provides a concise overview of the exclusive sulfide properties as a metal ligand, with emphasis on the structural aspects and biosynthesis. Sulfide as catalyst and as a substrate is discussed. Different enzymes are considered, including xanthine oxidase, formate dehydrogenases, nitrogenases and carbon monoxide dehydrogenases. The sulfide effect on the activity and function of iron‑sulfur, heme and zinc proteins is also addressed.