Familial mesial temporal lobe epilepsy (FMTLE) was first described as a benign syndrome with prominent psychic and autonomic seizures and no association with hippocampal sclerosis (HS) or febrile seizures (FS). Better definition of the syndrome allowed identification of more heterogeneous phenotypes with mild to severe epileptic disorders, and a variable association with HS and FS. The genetics of these conditions is largely unknown and the hope for the future is that the identification of FMTLE genes will lead to more appropriate approaches for the diagnosis and treatment of TLE.