Despite tension-type headache represents one of the most frequent and costly diseases in modern society only very little research on this disease has actually been carried out. In contrast to former belief tension-type headache is a separate entity that can and should be separated from migraine. No specific biochemical abnormalities have yet been identified but a reliable human model of tension-type headache has been developed by means of infusion of a NO-donor, glyceryl trinitrate. Myofascial factors and peripheral sensitization of nociceptors play an important role in the episodic form, and central sensitization has been demonstrated in the chronic form. As chronic tension-type headache usually evolves from the episodic form, prevention and reversal of this central sensitization may be an important target for future pathophysiological studies and drug development.