Improvement in the biomedical and biotechnological research fields have allowed refinement of the neuromodulation approach in the treatment of a subgroup of medical disorders otherwise refractory to pharmacological treatment, such as chronic primary headaches. Chronic pain conditions imply central sensitisations and functional reorganisation that cannot be quickly or easily reversed. It appears evident that conventional treatment can sometimes be unsuccessful or only partially successful, and that relapse is common. Cluster headache (CH) is the most frequent trigeminal autonomic cephalalgia (TAC) and the most representative of this spectrum of disorders characterised by the association of headache and loco-regional signs and symptoms of facial parasympathetic activation. The striking features of circadian rhythmicity of attacks and circannual periodicity of cluster period, together with the neuroendocrine abnormalities, are suggestive of a neurochronobiological disorder with a central-diencephalic pathogenetic involvement, confirmed by direct evidence in functional neuroimaging studies of ipsilateral posterior hypothalamic activation during cluster attack. In 2000 these findings prompted a functional neurosurgery approach, with the first case of deep brain hypothalamic stimulation (DBS) in a severely disabled chronic CH patient. Since then, 18 implants in our centre and many others in different countries have been performed. Although the outcomes are encouraging, the invasive nature of the technique and the occurrence of rare but major adverse events have suggested a safer peripheral approach with occipital nerve stimulation (ONS).