Hydrogen sulfide (H2S) is now admitted as a third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO), albeit it was originally considered as a foul and poisonous gas. Endogenous H2S production in mammalian cells is counting on the three enzymes acting on cysteine. Involvement of H2S in various physiological and pathological processes has been extensively studied in the last fifteen years. Mounting evidence suggests that H2S is able to protect against atherosclerosis development and progression. Exogenous H2S supplement has salutary effects on atherogenesis, and reduction of the endogenous H2S level accelerates atherosclerosis. The anti-atherosclerotic mechanisms of H2S have been descried in different aspects, including endothelium preservation, antioxidative action, anti-inflammatory responses, vasorelaxation, regulation of ion channels, etc. However, further investigation is still needed to help us gain more insights into the fundamental underlying mechanisms, and that will allow us to design better therapeutic applications of H2S in the treatment of atherosclerosis.