Stroke has become a more common disease worldwide. Despite great efforts to develop treatment, little is known about ischemic stroke. Cerebral ischemia activates multiple cascades of cell type-specific pathomechanisms. Ischemic brain injury consists of a complex series of cellular reactions in various cell types within the central nervous system (CNS) including platelets, endothelial cells, astrocytes, neutrophils, microglia/macrophages, and neurons. Diverse cellular changes after ischemic injury are likely to induce cell death and tissue damage in the brain. Since cells in the brain exhibit different functional roles at distinct time points after injury (acute/subacute/chronic phases), it is difficult to pinpoint genuine roles of cell types after brain injury. Many experimental studies have shown the association of apoptosis signal-regulating kinase 1 (ASK1) with cellular pathomechanisms after cerebral ischemia. Blockade of ASK1, by either pharmacological or genetic manipulation, leads to reduced ischemic brain injury and subsequent neuroprotective effects. In this review, we present the cell type-specific pathophysiology of the early phase of ischemic stroke, the role of ASK1 suggested by preclinical studies, and the potential use of ASK suppression, either by pharmacologic or genetic suppression, as a promising therapeutic option for ischemic stroke recovery.