We introduce some investigative approaches and findings on differential gene expression in human epileptic time as well as in animal models of epilepsy. Molecular alterations observed in the epileptic brain suggest that they may disclose different psychopathological stages. It is possible that different gene expression combinations involved in cell death, reactive oxygen metabolism, synaptic transmission and immune response and of neurotrophins reflect distinct functional properties of different neuronal and glial populations, which determine specific brain region responses. Understanding the molecular patterns of gene expression following epileptogenic insults will be of great importance for the development of treatments aiming to reduce neurotoxicity and subtle synaptic dyfunctions present in the early stages as well as during the chronic phase of epilepsy.