More than twenty years have passed since the demonstration of hydrogen sulfide (H2S) as a signaling molecule. Various roles of this molecule have been reported including neuromodulation, vascular relaxation, cytoprotection, anti-inflammation, and oxygen sensing. During the study of its effect on neuromodulation, we found TRP channels as a target of H2S, and later identified polysulfides (H2Sn) as chemical entity of the ligand. We found that H2S relaxes vasculatures in synergy with NO, and recently identified H2Sn as products produced by the chemical interaction between H2S and NO to exert the effect, suggesting that it may be a mechanism for the synergy between the two molecules. It has attracted attention that sulfite, a further metabolite of H2S and H2Sn, protects neurons from oxidative stress by a mechanism different from that by H2S and H2Sn.