Hydrogen sulfide (H 2S) is a Janus-faced molecule. On one hand, several toxic functions have been attributed to H 2S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H 2S delivery based clinical therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H 2S has been found to have pleiotropic effects on physiology and health. H 2S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addition to H 2S production by mammalian cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), H 2S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate reduction (DSR) pathway. In the gut, H 2S regulates functions such as inflammation, ischemia/ reperfusion injury and motility. H 2S derived from gut microbes has been found to be associated with gastrointestinal disorders such as ulcerative colitis, Crohn’s disease and irritable bowel syndrome. This underscores the importance of gut microbes and their production of H 2S on host physiology and pathophysiology.