The term spreading depolarization (SD) describes a wave of profound cellular depolarization in the brain’s gray matter. The hallmark of SD is the breakdown of ion homeostasis. Among the ionic changes, the net influx of calcium into neurons is of importance since it is assumed to induce the cascades leading to neuronal death. While short-lasting SDs are survived, long-lasting SDs are detrimental. SD has been studied extensively in animal models in vivo and in vitro for decades and has been shown lately to occur frequently in the early and delayed time period in patients with SAH. In this chapter, electrophysiological and imaging methods are described to record SD.