Hydrogen sulfide (H(2)S) 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 H(2)S 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 H(2)S. H(2)S-releasing agents (also known as H(2)S 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 H(2)S, and summarize the chemistry and biological activity of some natural and synthetic H(2)S donors. We introduce the developments of currently available H(2)S-releasing drugs including H(2)S-non-steroidal anti-inflammatory drugs, H(2)S-nervous system drugs and NO-H(2)S-releasing drugs. We hope this review will be a value reference in the development of H(2)S-releasing drugs in the treatment of cardiovascular and nervous diseases.