Cluster headache is a rare primary headache disorder and the most common trigeminal-autonomic cephalalgia. Even though it has been extensively studied, its pathophysiology remains nebulous. Over the last two decades, cerebral imaging has increasingly been used to aid the investigation of pain and headache disorders. Pioneering work using magnetic resonance-based, voxel-based morphometry depicted an isolated increase of grey matter in the posterior hypothalamus and thereby reconfirmed the most commonly accepted pathophysiological concept. More recent works demonstrate structural changes across multiple structures related to pain processing, sensory integration, and emotional evaluation. These changes do not seem to be static, but rather appear to be dynamic in nature as they change over the course of the disease. This was interpreted as a reflection of the plasticity of the human brain and should guide future thoughts towards a more complex pathophysiological model involving a maladaptive pain modulatory network.