Cortical spreading depression (CSD) is a slowly-moving suppression of electrical activity that travels across the cortex at a rate of 2-5 min-1. CSD is transient, and accompanied by a severe disruption of ion homeostasis, depolarization of nerve cells and enhanced energy metabolism. The slow march of migraine prodromes has many features in common with CSD. On this background it has been suggested that CSD is a mechanism of migraine. Recently, the notion has gained renewed credibility with the demonstration of unique abnormalities of brain blood flow, energy metabolism and magnetoencephalography during migraine attacks which have been replicated point-by-point in the animal model during CSD. Simultaneously, a series of experiments have indicated that CSD is closely linked to activity of the N-methyl-D-aspartate (NMDA)-subtype of the glutamate-receptor. It is suggested, that N-methyl-D-aspartate-antagonism could be the next bid of a rational migraine therapy.