Abstract: Hydrogen sulfide(H₂S)is an endogenous gas messenger molecule with extremely broad biological activities including vasodilation, anti-oxidation, anti-inflammation, cardioprotection and anti-tumor. Similar to other gas messenger molecules, the biological activity of H₂S is dependent on its location, concentration and duration of exposure. Therefore, the key scientific issue is how to improve the selectivity of H₂S donor molecules to release appropriate concentrations of H₂S at the target site(commonly pathological place), exerting therapeutic efficacy with limited side-effects. This article reviews the structures and H₂S release mechanisms of two classes of H₂S donors focusing on the advances in the recently developed H₂S donors with controllable release potential of H₂S, thus providing new ideas for future H₂S-based drug research.