Headaches are widespread recurrent or chronic pain disorders. Every aspect of daily life, from work performance to social and family relationships, can be severely affected and many individuals feel this problem is even more unbearable than the pain itself. The prehistoric era showed the first indications of a headache deemed so unbearable that a hole had to be drilled in the head. Indeed, cranial drilling is the oldest surgical operation, as attested by palaeopathological evidence. In the Neolithic period (7,500 - 5,300 BC) drilling was practised widely; the oldest drilled skull in Europe was found in Ensisheim, Alsace and in the Neolithic necropolis of Loisy-en-Brie (France), a drilled skull with a bone flap to close the hole was discovered. Examples of drilling can also be found in Italy, such as the Catignano skull dating back to the fifth millennium. These finds indicate how headaches have afflicted humankind since the earliest times: the notion that stress is typical of the contemporary world must be revised, while the idea that 'sickness of living' has affected humankind throughout its long history must be accepted. In the 4th century B.C. Hippocrates described a migraine with aura, while in the 1st century A.D. Areteus of Cappadocia codified a syndrome he called heterocrania, the symptoms of which were unilateral pain, nausea and vomiting. The term hemicrania was later coined by Galen, who attributed the disease to yellow bile, one of the four humours hypothesised by Hippocrates as responsible for the disease. Today’s clinical instruments can accurately measure disability parameters, whose significant reduction is increasingly the focus of drug trial end-points.