Cerebral ischemia, a pathological condition in which brain tissue experiences a shortage of cerebral blood flow, is associated with cerebrovascular disease, brain trauma, epilepsy, and cardiac arrest. A reduction in blood flow leaves the brain tissue unsupplied with oxygen and glucose, thus leading to cell death in the ischemic core as well as subsequent peripheral injury in the penumbra. Neurons in the penumbra, where reperfusion occurs, are functionally inactive but still viable. Many biochemical changes, which may lead to neuronal cell death, thereby induce dysfunction of the central nervous system. However, the mechanisms responsible for ischemic stroke-induced cell damage remain to be determined. Protein phosphorylation has been implicated in the regulation of diverse cellular responses in the brain. Initially, tyrosine phosphorylation was considered to be involved in the regulation of cell growth and development. In addition, a variety of synaptic and cellular functions mediated by tyrosine phosphorylation in the brain were found to be associated with relatively high levels of protein tyrosine kinase activity. However, the involvement of this protein tyrosine kinase activity in ischemic cell death is still not fully understood. This review summarizes recent advances dealing with the possible implications of protein tyrosine phosphorylation in the ischemic brain.