A proportion of episodic migraine patients experiences a progressive increase in attack frequency leading to chronic migraine (CM). The most frequent external factor that leads to headache chronification is medication overuse. The neurobiological bases of headache chronification and of the vicious circle of medication overconsumption are not completely elucidated. More recently, the same neurophysiological methods used to study episodic migraine were applied to CM and medication-overuse headache (MOH). Studies of cortical responsivity tend overall to indicate an increase in excitability, in particular of somatosensory and visual cortices, reflected by increased amplitude of evoked responses, decreased activity of inhibitory cortical interneurons reflected in the smaller magnetic suppression of perceptual accuracy, and, at least for visual responses, an increase in habituation. In MOH, overconsumption of triptans or NSAIDs influences cortical excitability differently. Generalized central sensitization is suggested to play an important role in the pathophysiology of headache chronification.