Functional imaging studies had previously demonstrated specific activation of the brainstem in episodic migraine and the posterior hypothalamus in cluster headache (CH). The studies by the Headache Group helped further refine the localisation of the brainstem activation in episodic and chronic migraine to the dorsal rostral pons using positron emission tomography (PET) and demonstrated that lateralisation of pain in migraine is due to lateralised brain dysfunction. We also studied cerebral activation patterns in paroxysmal hemicrania (PH) and short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), which along with CH are grouped together as trigeminal autonomic cephalalgias. Significant activation of the posterior hypothalamus and ventral midbrain region was demonstrated in PH using PET while posterior hypothalamic activation was demonstrated in SUNCT using functional magnetic resonance imaging. In a PET study in hemicrania continua (HC), the clinical phenotype of which overlaps with migraine and the trigeminal autonomic cephalalgias, we demonstrated significant activation of the posterior hypothalamus, dorsal rostral pons and ventrolateral midbrain. These series of studies suggested that primary headache may be pathophysiologically differentiated on the basis of distinct patterns of brain activation, with hypothalamic and dorsal pontine activation as markers of trigeminal autonomic cephalalgias and migrainous syndromes, respectively. These studies draw attention to the structures that may play a pivotal role in the pathophysiology of primary headaches. The classification and clinical spectrum of headache disorders have hitherto been poorly defined though large strides have been made in this area over the last two decades. We has accumulated relatively large cohorts of various headaches syndromes and systematically studied their clinical phenotypes.