Stroke is a kind of acute cerebrovascular disease characterized by the focal lack of neurological function, including ischemic stroke and hemorrhagic stroke. As society ages rapidly, stroke has become the second leading cause of disability and death, and also become the main threat to human health and life. In recent years, findings from increasing animal and clinical trials have supplied scientific evidences for the treatment of stroke. Hydrogen sulfide (H2S), which has always been seen as a toxic gas, now has been thought to be the third gaseous signaling molecule following nitric oxide and carbon monoxide. Accumulating evidences indicate that H2S plays an important role in stroke. Given that its neuroprotective effect is dose-dependent, only when its concentration is relatively low, H2S can yield the neuroprotection, while high dose may lead to neurotoxicity. All these study results suggest that H2S may offer a new promising application for the therapy of stroke. Here, our review will present the role of H2S in stroke from its mechanism to animal and clinical studies.