Cortical spreading depression (CSD) is thought to be the electrophysiological correlate of migrainous aura, thus its modulation might revail further details of migraine pathomechanism. We summarize scientific data from previous animal experiments regarding CSD modulation.The characteristics of KCl induced CSD waves were examined after various pretreatments (migraine prophylactic drugs, kinurenines, gonadal hormones) in rats.Lamotrigine was able to supress CSD-s, while valproic acid decreased only its propagation velocity. In other experiments kynurenic acid, an endogenous glutamate antagonist proved to be effective in the reduction of rat CSD waves. Both progesteron and estradiol pretreatment increased the CSD frequency.Some of the migraine prophylactic drugs are able to modulate CSD, but others not, which suggests that these medications act at different levels of migraine genesis. The suppressing effect of kynurenines is possibly related to their anti-glutamatergic action. Interestingly female gonadal steroids have a marked effect on CSD generation, which might be linked to the strong sexual dimorphism of migraine headache.