Hydrogen sulfide (H₂S) is now recognized as the third “gasotransmitters” along with nitric oxide (NO) and carbon monoxide (CO) and has been proved to have many biological effects, such as vasodilation, neuroprotection, circadian rhythm regulation and anti-aging. Recent studies have revealed an independent mitochondrial H₂S synthesis pathway, which is different from the cytoplasmic H₂S synthesis mediated by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL or CSE). It has been reported that two mitochondrial targeted H₂S donors AP39 and AP123 show stronger cell protection and less cytotoxicity than classical inorganic salt donor NaHS, indicating the particularity of mitochondrial H₂S. This review mainly introduced mitochondrial H₂S about its generation, metabolism and effects on mitochondria. Recent progress of the new mitochondrial targeting H₂S donors are also discussed in this paper, in order to provide a more comprehensive understanding of hydrogen sulfide.