The subiculum has for a long time been neglected and solely considered as the output region of the hippocampus, conducting or relaying inputs to the entorhinal cortex. However, significant evidence does not support such a passive role. The subiculum is a three-layer cortex structured associated with highly organized substructures. Preeminent bursting neuronal behavior and local microcircuits favor the production of strong neuronal activities. All hippocampal rhythms such as theta, gamma, sharp-wave ripples, and ripples can be generated by the subiculum. As a result, the subiculum is an important limbic structure involved in spatial location and memory. The role of the subiculum in epilepsy was highlighted by studies on human postoperative tissues, showing that it is a major and autonomous site of genesis of epileptic interictal and ictal activities. In these studies, a leading role of interneurons in the buildup of epileptic activities was suggested, and chloride dysregulation leading to depolarizing and potentially excitatory effects of GABAA signaling was unraveled. Evidence indicates that the subiculum not only anatomically “supports” hippocampal outputs, but that it also actively participates to the generation of epileptic activities in the temporal lobe.