While primary, or idiopathic, epilepsies may exist, in the vast majority of cases epilepsy is a symptom of an underlying brain disease or injury. In these cases, it is difficult if not impossible to dissociate the consequences of epilepsy from the consequences of the underlying disease, the treatment of either the disease or the epilepsy, or the actual seizures themselves. Several cases of apparent complications of epilepsy are presented to illustrate the range of consequences encountered in clinical practice and the difficulty in assigning blame for progressive symptomatology in individual cases. Because of the difficulty in interpreting clinical material, many investigators have turned to epilepsy models in order to address the potential progressive consequences of recurrent seizures. The authors review experimental data, mainly from animal models, that illustrate short-, medium-, and long-term morphological and biochemical changes in the brain occurring after seizures, and attempt to relate these observations to the human condition.