Abstract: Stroke is one of the diseases that seriously endanger human health without effective treatment at present, due to the lack of in-depth understanding of the cellular and molecular mechanisms underlying neuronal cell death after ischemia. In the present article, in order to lay the foundations for the development of therapeutic regimens for ischemic stroke, we review the underlying pathophysiology of ischemic stroke including apoptosis, excitotoxicity, oxidative and nitrative stress, inflammation, innate and adaptive immune cells, the gutmicrobiota and intracranial atherosclerosis, and reveal the intertwinedpathways that are promising therapeutic targets.