Despite great progresses in the treatment and prevention of ischemic stroke, it is still among the leading causes of death and serious long-term disability all over the world, indicating that innovative neural regenerative and neuroprotective agents are urgently needed for the development of therapeutic approaches with greater efficacy for ischemic stroke. More and more evidence suggests that a spectrum of epigenetic processes play an important role in the pathophysiology of cerebral ischemia. In the present review, we first discuss recent developments in epigenetic mechanisms, especially their roles in the pathophysiology of cerebral ischemia. Specifically, we focus on DNA methylation, histone deacetylase, histone methylation, and microRNAs (miRNAs) in the regulation of vascular and neuronal regeneration after cerebral ischemia. Additionally, we highlight epigenetic strategies for ischemic stroke treatments, including the inhibition of histone deacetylase enzyme and DNA methyltransferase activities, and miRNAs. These therapeutic strategies are far from clinic use, but preliminary data indicate that neuroprotective agents targeting these pathways can modulate neural cell regeneration and promote brain repair and functional recovery after cerebral ischemia. A better understanding of how epigenetics influences the process and progress of cerebral ischemia will pave the way for discovering more sensitive and specific biomarkers and new targets and therapeutics for ischemic stroke.