A review of the literature reveals an impressively broad spectrum of effects of the hormone estrogen in the CNS. One of the more recently documented is the ability of estrogen to protect neurons from cell death associated with a variety of insults. While some of these actions can be attributed to nuclear effects of the hormone, mediated by the estrogen receptors alpha and/or beta, an increasing number of these effects appear to result from actions of the hormone mediated by signal transduction pathways traditionally associated with activation of membrane receptors. Here, we review current findings on actions of estrogen mediated by two pathways: those dependent on cAMP and Protein Kinase A, and those related to activation of the Mitogen Acivated Protein Kinase cascade. The evidence that estrogen can rapidly activate either pathway, and the potential involvement of the estrogen receptors alpha or beta acting in the vicinity of the cell membrane will be discussed. The possible role of MAP-Kinase activation and BCL-2 induction in the phenomenon of estrogen-neuroprotection will also be addressed.