Hydrogen sulfide (H(2)S) has historically been considered to be a toxic gas, an environmental and occupational hazard. However, with the discovery of its presence and enzymatic production through precursors of L-cysteine and homocysteine in mammalian tissues, H(2)S has recently received much interest as a physiological signaling molecule. H(2)S is a gaseous messenger molecule that has been implicated in various physiological and pathological processes in mammals, including vascular relaxation, angiogenesis, and the function of ion channels, ischemia/reperfusion (I/R), and heart injury. H(2)S is an endogenous neuromodulator and present studies show that physiological concentrations of H(2)S enhance NMDA receptor-mediated responses and aid in the induction of hippocampal long-term potentiation. Moreover, in the field of neuronal protection, physiological concentrations of H(2)S in mitochondria have many favorable effects on cytoprotection.