Although electroconvulsive therapy (ECT) is a highly effective form of treatment, its use is limited by the emergence of cognitive side effects, notably anterograde and retrograde amnesia. Despite a large literature on the neurobiology of therapeutic mechanisms of ECT, very little is known about the neurobiological underpinnings of its cognitive effects. On theoretical grounds, structures within the medial temporal lobes, especially the hippocampus, are predicted to be critical regions mediating anterograde and, possibly, retrograde amnesia. However, functional neuroimaging studies in normal volunteers have demonstrated that frontal cortical regions are also involved in human memory processes. This review will highlight some of the biochemical, electrophysiological, and neuroimaging correlates of the amnestic side effects of ECT. In terms of electrophysiological and functional imaging studies, there are data that implicate both medial temporal and frontal regions as being associated with cognitive dysfunction. Interestingly, such data also appear to indicate a dissociation of the neural systems critical to the efficacy and adverse cognitive effects of ECT.