Understanding of the mechanisms of estrogen action in the brain has always been poor. Neurons in several brain regions do not harbor estrogen receptor alpha (ERalpha) and yet are estrogen responsive. It was formerly thought that these responses represented indirect actions of estrogen. It is now evident that these neurons express ERbeta and that estrogen receptors have diverse actions in the central nervous system. By clear delineation of the cellular expression and function of the two estrogen receptors, it is likely that, in the future, selective ERalpha and ERbeta ligands will be developed and used for treatment of depression and behavioral disorders and may be useful in preventing degenerative diseases, such as Alzheimer's and Parkinson's disease.