Epilepsy has been known since antiquity and trepanation has been documented as a therapeutic option. The Greek born physician Aretaeus of Cappadocia (2nd century BC) was the first to recommend trepanation for the treatment of refractory epilepsy to drugs, pointing out the efficacy of the method (Fig. 1). Trepanation was practiced throughout the Middle Ages, as it is proved by the book of "Quattuor Magistri" and during Renaissance as well. In 19th century, Sir Victor Alexander Horsley (1857-1916), combining analysis of clinical presentation with cortical stimulation, performed a series of craniotomies for the treatment of epilepsy Fig. 2. In the following years the advent of electrophysiology and neurosurgery provided a fertile ground for further progress in epilepsy surgery such as the preoperative use of electroencephalography (EEG) to determine the epileptogenic zone by Otfrid Foerster (1873-1941); the research of Wilder Graves Penfield (1891-1976) in Montreal Neurological Institute and the use of stereoelectroencephalography (SEEG) by the neurosurgeon Jean Talairach (1911-2007) and the neurologist Jean Bancaud (1921-1994)) Fig. 3. Nowadays, epilepsy surgery remains a valuable therapeutic option in cases of drug resistant epilepsy.