Hydrogen sulfide (H2S), produced enzymatically, acts as a signaling molecule involved in the regulation of neurotransmission, vascular tone, cytoprotection, inflammation, oxygen sensing, and energy metabolism. Hydrogen polysulfides (H2Sn, n > 2) and other per- and polysulfides, such as cysteine persulfide, are enzymatically produced to regulate target protein activity. The chemical interaction of H2S with NO also generates H2Sn. S-sulfuration (S-sulfhydration) has been proposed as a mode of action of H2S to regulate the activity of target molecules. H2Sn S-sulfurate cysteine residues, while H2S S-sulfurates oxidized cysteine residues such as those S-nitrosylated and S-sulfinated. Transient receptor potential ankyrin 1 (TRPA1) channels, which convert stimulations such as pain, pressure, and temperature to the neuronal signal, were identified as a target of H2Sn. Recently the channels were found to be involved in the regulation of the transcription/translation of sulfur metabolizing enzymes and the intracellular levels of sulfur containing amino acids, cysteine and methionine, and even those of neurotransmitter GABA. The physiological roles of these molecules will be discussed.