Inflammation is a normal adaptive response to traumatic, infectious, post-ischemic, toxic or autoimmune injury. Uncontrolled inflammation, however, results in disease, and most of diseases have been shown to have an inflammatory component. Identifying biological molecules that mediate inflammation, and strategies that could control inflammation, therefore, can lead to novel therapeutic approaches for several diseases. Hydrogen sulfide (H2S), a toxic gas, has been known as an environmental and industrial pollutant for more than 300 years. In recent years, however, it has been shown to be produced in the human body. We have shown that H2S, synthesized by the activity of cystathionine-γ-lyase (CSE), acts as a mediator of inflammation in different disease conditions. Based on the studies with experimental models of disease, which have been substantiated by recent clinical studies, we now have a good understanding of the contribution of H2S to inflammation. Awareness of a new mediator of inflammation, which can be inhibited as a potential therapeutic approach for inflammatory disease, presents numerous opportunities. This is a new area of research with immense promise, both in terms of understanding the pathology of inflammation, and discovering new treatments for diseases which are major health problems.