Hydrogen sulfide (H 2S) is a well known and pungent toxic gas that has recently been shown to be synthesised in man from the amino acids cystathionine, homocysteine and cysteine by at least two distinct enzymes; cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H 2S has emerged as a novel and increasingly important mediator in the cardiovascular system but delineating the precise physiology and pathophysiology of H 2S is proving to be complex and difficult to unravel with disparate findings reported with cell types, tissue types and animal species reported. Therefore, in this review we summarize the mechanisms by which H 2S has been proposed to regulate blood pressure and cardiac function, discuss the mechanistic discrepancies reported in the literature as well as the therapeutic potential of H 2S. We also examine the methods of H 2S detection in biological fluids, processes for H 2S removal and discuss the reported blood levels of H 2S in man and animal models of cardiovascular pathology. We also highlight the complex interaction of H 2S with nitric oxide in regulating cardiovascular function in health and disease.