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Observations in the 1990s ascribed physiological actions to H<jats:sub>2<\/jats:sub>S in the nervous system, proposing that this gasotransmitter acts as a neuromodulator. Soon after that, the vasodilating properties of H<jats:sub>2<\/jats:sub>S were demonstrated. In the past decade, H<jats:sub>2<\/jats:sub>S was shown to exert a multitude of physiological effects in the vessel wall. H<jats:sub>2<\/jats:sub>S is produced by vascular cells and exhibits antioxidant, antiapoptotic, anti-inflammatory, and vasoactive properties. In this concise review, we have focused on the impact of H<jats:sub>2<\/jats:sub>S on vascular structure and function with an emphasis on angiogenesis, vascular tone, vascular permeability and atherosclerosis. H<jats:sub>2<\/jats:sub>S reduces arterial blood pressure, limits atheromatous plaque formation, and promotes vascularization of ischemic tissues. Although the beneficial properties of H<jats:sub>2<\/jats:sub>S are well established, mechanistic insights into the molecular pathways implicated in disease prevention and treatment remain largely unexplored. Unraveling the targets and downstream effectors of H<jats:sub>2<\/jats:sub>S in the vessel wall in the context of disease will aid in translation of preclinical observations. In addition, acute regulation of H<jats:sub>2<\/jats:sub>S production is still poorly understood and additional work delineating the pathways regulating the enzymes that produce H<jats:sub>2<\/jats:sub>S will allow pharmacological manipulation of this pathway. 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