The concept of catamenial epilepsy is strengthened by the finding that the periodicities of seizure occurrence vary with the ovulatory status of the menstrual cycle. Additionally, catamenial epilepsy may be significantly more common with a left-sided unilateral temporal epileptic electroencephalogram (EEG) focus as compared to a right-sided temporal focus. This chapter presents a model in which estradiol generally has neuroexcitatory and proconvulsant effects whereas progesterone has reduced metabolites with potent neuroinhibitory and anticonvulsant effects, a model that appears to be most consistent with clinical observations. Progesterone treatment has taken two forms: cyclic progesterone therapy which supplements progesterone during the luteal phase and withdraws it gradually premenstrually and suppressive therapy in which the goal is to suppress the menstrual cycle which is generally accomplished using injectable progestins or gonadotropin releasing-hormone analogues.