In trying to rectify the differences in the risk, onset, and progression of neurodegenerative diseases between men and women, the gonadal hormone estrogen has been the primary focus of investigation for many years. Although this gender difference may encompass disparate and overlapping reasons, estrogen and signaling events mediated by its receptor have been shown to be neuroprotective in a number of neurodegenerative disease models such as Alzheimer's, Parkinson's, and Schizophrenia. Although data from human studies remains highly controversial, a large body of research findings suggests that this hormone plays a pivotal role in retarding and preventing the formation of neurodegenerative diseases through its receptor. By activating common intracellular signaling pathways and initiating "cross talk" with neurotrophins, estrogen plays an influential role in neuronal survival from injuries induced by ischemia or other environmental insults. Gaining a better understanding of these estrogen receptor mediated neuroprotective mechanisms may lead to new therapeutic strategies for the treatment or prevention of neurodegenerative diseases.