Abstract: Hydrogen sulfide (H₂S) is considered as a new member of gasotransmitter family, following nitric oxide (NO) and carbon monoxide (CO). H₂S exerts important biological effects in mammals, which has drawn more and more attention in recent years. It is proved that H₂S has a role in the regulation of physiological and pathophysiological processes in the cardiovascular system and the nervous system. Several cardiovascular and nervous diseases are connected to H₂S. H₂S-releasing agents (also known as H₂S donors) have been widely used not only as useful research tools but also potential therapeutic agents. In this review, we provide an overview of the chemistry and biology of H₂S, and summarize the chemistry and biological activity of some natural and synthetic H₂S donors. We introduce the developments of currently available H₂S-releasing drugs including H₂S-non-steroidal anti-inflammatory drugs, H₂S-nervous system drugs and NO-H₂S-releasing drugs. We hope this review will be a value reference in the development of H₂S-releasing drugs in the treatment of cardiovascular and nervous diseases.