Timely reperfusion is critical for salvaging ischemic tissue in myocardial infarction, in stroke, and during resuscitation. Paradoxically, the reperfusion of blood into the ischemic organ is damaging in itself, leading to ischemia/reperfusion (IR) injury. Best clinical practice is to reperfuse rapidly to limit ischemic time. Despite this, extensive IR injury still occurs, which is a major driver of pathology, making the prevention of this damage a clear unmet clinical need.1 Recent work has shown a role for mitochondrial succinate metabolism in IR injury that opens up exciting new therapeutic approaches.