Single-photon emission computed tomography is a well established functional imaging technique in epilepsy that aids precise noninvasive localization of the seizure focus required for surgical intervention in refractory seizures. Electroencephalography with video monitoring of seizures precedes more invasive evaluation, such as cortical or depth electrodes. Positron emission tomography studies in temporal lobe epilepsy are moderately sensitive, demonstrating ipsilateral hypometabolism. Ictal single photon emission computed tomography studies in temporal lobe epilepsy demonstrate transient intense hyperemia in the anterior temporal lobe structures. Peri-ictal images show persisting mesial temporal hyperperfusion with lateral hypoperfusion developing over the next 2 to 5 minutes to be replaced by significant hypoperfusion in the postictal phase. Interictal single photon emission computed tomography with ipsilateral hypoperfusion, suffers from reduced sensitivity and accuracy, whereas ictal and, to a lesser extent, peri-ictal and postictal single photon emission computed tomography are highly sensitive and accurate in localizing temporal lobe epilepsy. New iodinated neuroreceptor single photon emission computed tomography imaging agents hold promise in localizing the seizure focus (focally reduced uptake) without ictal injection, and also may elucidate underlying mechanisms inherent to epilepsy.