 Mitochondrial reactive oxygen species, MROS, play a key role in the pathophysiology of ischemic organ injury. The generation of MROS during ischemia slash reperfusion, I-slash-R, leads to cellular damage and infarction. Several pharmacological agents have been developed to target MROS production and protect against I-slash-R induced injury. These include agents that target potassium channels, such as KATP channel modulators and BKCA channel blockers, which induce cell survival programs and reduce post ischemia tissue injury. Additionally, novel strategies are being explored to specifically target MROS production for the prevention of myocardial dysfunction and infarction, and the reduction of neurocognitive deficits and neuronal cell death in stroke. This article was authored by Theber Kolodras, Imin Bao, and Ronald J. Corthuis.