Hydrogen sulfide (H S) is a ubiquitous signaling molecule with important functions in many mammalian organs and systems. Observations in the 1990s ascribed physiological actions to H S in the nervous system, proposing that this gasotransmitter acts as a neuromodulator. Soon after that, the vasodilating properties of H S were demonstrated. In the past decade, H S was shown to exert a multitude of physiological effects in the vessel wall. H 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 S on vascular structure and function with an emphasis on angiogenesis, vascular tone, vascular permeability and atherosclerosis. H S reduces arterial blood pressure, limits atheromatous plaque formation, and promotes vascularization of ischemic tissues. Although the beneficial properties of H 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 S in the vessel wall in the context of disease will aid in translation of preclinical observations. In addition, acute regulation of H S production is still poorly understood and additional work delineating the pathways regulating the enzymes that produce H S will allow pharmacological manipulation of this pathway. As the field continues to grow, we expect that H S-related compounds will find their way into clinical trials for diseases affecting the blood vessels.