Hydrogen sulfide, (H2S), is an endogenous gas which exerts a protective function in several biological processes, including those involved in inflammation, blood pressure regulation, and energy metabolism. The enzymes involved in H2S production are cysthationine -synthetase, cysthationine -lyase and 3-mercaptopyruvate sulfurtransferase. Low plasma H2S levels have been found in chronic renal failure (CRF) in both humans and animal models. The mechanisms leading to H2S deficiency in CRF are linked to reduced gene expression of cysthationine -lyase. Intense research is currently under way to discover the link between low H2S levels, CRF progression and the uremic syndrome and to determine whether therapeutic interventions aimed at increasing H2S levels might benefit these patients.