Migraine is a neurovascular disorder, characterized by episodes of throbbing headache, vegetative symptoms and prodromal focal symptoms in a minority of cases. The neuronal basis of migraine has been fully recognized since many years. The initial hypothesis of a basal hyper-excitability generating Cortical Spreading Depression (CSD) and the consequent trigemino-vascular system activation was a matter of debate. Neurophysiological evidence suggested a more complex change of neuronal excitability, based on altered thalamus-cortex modulation and modification of neuronal network oscillations. The “oscillopathy” characterizing migraine is well represented by functional connectivity methods , showing abnormalities in default mode and stimulus related networks. How these basal neuronal abnormalities could lead to CSD is still unknown. However, the phenomenon of CSD seems peculiar of migraine and not simply attributable to neuronal hyper-excitability, though the transient depolarization could produce synaptic plasticity and progressive functional changes.