The headache is a very frequent symptom and represents the 0.36%-2.5% of all reasons of claim to Emergency Department. Even if it is rarely related to high risk diseases, it is mandatory to promptly differentiate life-threatening conditions. In order to establish a correct diagnostic and therapeutic pathway and ask for aimed specialistic consultation, the emergency physician must be familiar with the various categories of headache. It is important to distinguish between essential headache and secondary headache. All patients presenting to the emergency department with the complaint of headache should be interviewed carefully regarding their history. The quality of pain associated with the intensity, location, rate, duration, modality of onset, relieving or worsening conditions, response to drugs, symptoms or signs associated must be investigated as well. Careful neurological examination including the vision of fundus oculi and the evaluation of rigor nucalis can provide further important diagnostic information. Laboratory exams do not usually give significant issues in the majority of patients with headache. However, dosage of inflammation index can be useful when an infective or inflammatory disease is suspected. CT scan can rule-out the suspicion of organic intracranial causes. When the physician suspects meningitis or subarachnoid hemorrhage (SAH) not showed by CT scanning, rachicentesis can turn out diagnostic. The modality of onset, clinical characteristics and differential diagnosis of subarachnoid hemorrhage, intracranial hypertension, colloidal cyst of the third ventricle, trigeminal neuralgia, temporal arteritis and pituitary adenomas and apoplexy will be discussed. These diseases are not only of neurological and neurosurgical interest, but involve also the physician in the Emergency Department.