Hydrogen sulfide (H(2)S) has emerged as the third endogenous gaseous mediator in the central and peripheral nervous system. H(2)S is generated by three enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). In the CNS, H(2)S, generated mainly by CBS in astrocytes and 3MST in neurons, appears to participate in cognition, memory, regulation of the cardiopulmonary functions and neuroprotection. In the peripheral nervous system, evidence suggests that H(2)S may be involved in autonomic control of the cardiopulmonary and gastrointestinal functions as well pain and inflammation.