Estrogen is regulated through two intracellular receptors, estrogen receptor alpha and estrogen receptor beta, through a classic nuclear-initiated response. Recently, estrogen has also been shown to act more rapidly and it is proposed that these fast effects may be the consequence of membrane localized estrogen receptors that act through the second messengers. Although the identification of these receptors remains to be elucidated, the possible role that they play in female-specific mood disorders is of particular interest, especially in times of major hormonal fluctuation. The purpose of this mini-review is to outline the recent literature regarding the rapid effects of estrogen, to explore the intracellular signaling pathways that may be involved in this regulation as well as the connection between estrogen and serotonin neurotransmission and finally, to look into the antidepressant role that estrogen may have, with particular emphasis on female-specific mood disorders.