Catamenial epilepsy is defined by the cyclical seizure exacerbation seen in almost 40% of women with epilepsy. The pattern appears to be related to predominance of estrogen over progesterone during the pre-ovulatory and/or perimenstrual days of the ovulatory menstrual cycle or during the broad period between day 14 and menstruation in anovulatory cycles with inadequate luteal progesterone levels. Progesterone affects central nervous excitability in an "inhibitory" manner, slowing kindling and decreasing seizure susceptibility in animal models. Estrogen enhances kindling and decreases after discharge threshold. These neurosteroidal hormones alter the GABA-A receptor in cell cultures and in animal models. Treatment of this clinical syndrome has been empirical and reported in a small series of women. Progesterone therapy and possible new approaches with synthesized neurosteroids may offer a promising approach to improve seizure control in women with catamenial epilepsy.