Hydrogen sulfide (H2S) is best known as a rather smelly gas. However, H2S is generated within the vascular wall and is able to transfer SH to susceptible cysteine residues in target proteins. This persulfidation or S-sulfhydration then alters protein function partly by rearranging disulfide bonds to affect protein conformation or their ability to dimerise. The IVS team has established a novel mass spectrometry–based method to map the S-sulfhydrome (unbiased identification of cysteine residues modified by H2S) in different cells and tissues. Currently, we are investigating the mechanisms driving the dynamics of S-sulfhydration that control endothelial cell fate decisions in health and diseases as well as the role of H2S-generating enzymes in the maintenance of cardiomyocyte function and cardiovascular health.