Reactive oxygen species have been implicated in brain injury after cerebral ischemia. These oxidants can damage proteins, lipids, and DNA, and lead to cell injury and necrosis. Oxidants are also initiators in intracellular cell death signaling pathways that may lead to apoptosis. The possible targets of this redox signaling include mitochondria, death membrane receptors, and DNA repair enzymes. Genetic manipulation of intrinsic antioxidants and the factors in the signaling pathways has provided substantial progress in understanding the mechanisms in cell death signaling pathways and involvement of oxygen radicals in ischemic brain injury. Future studies of these pathways may provide novel therapeutic strategies in clinical stroke.