Cases of amnesia following unilateral temporal lobe surgery are rare, but they may provide important insights into human brain functioning. Such cases are reconsidered here in the light of recent developments in clinical and cognitive neuroscience. Descriptions of preoperative seizure activity in these cases indicate the potentially valuable role of ictal semiology in localizing the source of epileptiform discharges. Cases of amnesia after unilateral temporal lobectomy illustrate the complexity of intra- and inter-hemispheric propagation of epileptiform discharges and highlight possible neurophysiological mechanisms underlying false localization of abnormal EEG activity. This review points to the value of preoperative neuropsychological assessment in providing information on the likely primary locus of pathology and in predicting outcome after surgery. The analysis of cases upholds the benefits of the Wada procedure, but it highlights the variability in Wada test procedures and the fact that Wada test scores themselves may be open to varying interpretation. These cases of postoperative amnesia are further considered in the context of the cognitive neuroscience of human memory and, in particular, mechanisms underlying the human amnesic syndrome. They confirm the critical role of bilateral medial temporal lobe structures in anterograde memory, but they also highlight the complexity in teasing apart neural mechanisms underlying remote memory loss.