Intracranial recordings from patients with medically refractory partial epilepsy have demonstrated that the concept of a discrete epileptic focus, as derived from experiments with animals, does not exist in this human condition. Furthermore, an EEG spike focus, as defined by electroencephalographers, does not faithfully identify the site of ictal onset. Rather, the boundaries of an epileptogenic region, which is necessary and sufficient for generation of habitual spontaneous seizures, must be approximated by knowledge of the spatial distribution of interictal spike discharges, and ictal onset, as well as the location of an epileptogenic lesion demonstrated by structural imaging, and the location and extent of nonepileptic focal functional deficits. Delineation of an epileptogenic region is confounded by the fact that epileptically and nonepileptically abnormal brain tissue also exists beyond this area and may even involve the contralateral hemisphere. Investigations of epileptic patients during the course of surgical treatment have led to an improved understanding of the persistent neuronal disturbances that predispose to the generation of spontaneous seizures, as well as disturbances in adjacent and distant tissues that receive ictal propagation and demonstrate interictal epileptiform and nonepileptiform abnormalities. The results of such studies will greatly enhance our ability to interpret scalp-recorded EEG transients and to devise better, noninvasive, diagnostic tools to accurately define the epileptogenic region.