Valproate has been shown to be an effective prophylactic treatment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. There is experimental evidence that it suppresses neurogenic inflammation and directly attenuates nociceptive neurotransmission. In addition, valproate reportedly alters levels of excitatory and inhibitory neurotransmitters and exerts direct effects on neuronal membranes in vitro. Valproate‘s observed effect may ultimately result from a combination of actions at different loci.