The histologic substrates of epilepsy can be divided into five major categories: tumor, disorders of neuronal migration and cortical organization, vascular malformation, mesial temporal sclerosis, and neocortical sclerosis secondary to brain injury. Magnetic resonance imaging is the most sensitive and specific imaging technique for the noninvasive identification of each of these epileptogenic substrates. Introduction of magnetic resonance imaging into clinical practice over the past 10 years has significantly changed the management of patients with epilepsy. It has also begun to redefine the classification of the epilepsies in terms of histologic substrates. This article focuses on the clinical role of magnetic resonance imaging in symptomatic epilepsy, the histologic substrates of epilepsy, and their magnetic resonance image appearance.