Hydrogen sulfide (H(2)S) has been found to play an important role as a signal molecule in regulating cell survival. It appears paradoxical that, on one side, H(2)S acts as a physiological intercellular messenger to stimulate cell growth, and on the other side, it may display cytotoxic activity. This article summarizes the current body of evidence demonstrating the cytoprotective versus cytotoxic effects of H(2)S in mammalian cells and describes the janus-faced properties of this important gasotransmitter. This article will also provide a brief description of the current signaling mechanisms that have been demonstrated to be responsible for these different actions. The pharmacologic regulation of H(2)S production and the potential clinical significance of H(2)S are highlighted.