We know by now that most types of cells in our body, if not all, possess H₂S-generating systems, from different types of enzymes to their substrates. Cellular H₂S production and metabolism are tightly and precisely regulated depending on cell types and metabolic particulars. Endogenously produced H₂S exerts profound impacts on physiological functions at cellular, tissue, system, and whole body levels. These acts ofH₂S are mediated by different molecular targets, such as different ion channels and signaling proteins. In addition to its direct interaction with thiol-containing proteins, H₂S also affects other signaling processes. Redox balance is one example of these processes. Alterations of H₂S metabolism lead to an array of pathological disturbances in the form of hypertension, atherosclerosis, heart failure, diabetes, cirrhosis, inflammation, sepsis, neurodegenerative disease, erectile dysfunction, and asthma, to name a few. By directing endogenous H₂S metabolism or applying exogenous H₂S, we may find novel solutions for preventing, interfering, and treating a wide spectrum of diseases.