The most prevalent primary headaches tension-type headache and migraine are frequently associated with neck pain. A wide variety of treatment options is available for people with headache and neck pain. Some of these interventions are recommended in guidelines on headache: self-management strategies, pharmacological and non-pharmacological interventions. Physical treatment is a frequently applied treatment for headache. Although this treatment for headache is predominantly targeted on the cervical spine, the neurophysiological background of this intervention remains unclear. Recent knowledge from neuroscience will enhance clinical reasoning in physical treatment of headache. Therefore, we summarize the neuro- anatomical and—physiological findings on headache and neck pain from experimental research in both animals and humans. Several neurophysiological models (referred pain, central sensitization) are proposed to understand the co-occurrence of headache and neck pain. This information can be of added value in understanding the use of physical treatment as a treatment option for patients with headache and neck pain.