Cortical spreading depression (CSD) is a transient (60-120 s) and at 3-5 mm/min propagating depolarization wave of cortical neurons and glial cells and is characterized by a DC shift of 20-35 mV. It is accompanied by massive redistribution of ions between extracellular and intracellular compartments and by a water influx into the cells. Extracellular potassium ion concentration increases up to 60 mM/l. Potassium ions and the excitatory neurotransmitter glutamate essentially contribute to the initiation and propagation of CSD. Both depolarization and disturbance of brain ion homeostasis regenerate within a few minutes while enhancing energy metabolism, but do not cause damage to normally perfused brain tissue. The similar propagation velocity of CSD and visual scotoma during migraine aura led to the assumption that CSD could be the underlying mechanism of migraine aura. The observation of CSD waves in migraine aura patients with the magnet encephalogram (MEG) technique confirmed this theory. Although many data support the relationship between CSD and aura phase in migraine, the role of CSD in migraine headache is still disputed.