Further studies to elucidate whether the nongenomic and genomic signaling pathways induced by estrogen in the brain display crosstalk or are separate regulatory pathways are also needed, as well as a careful determination of the contribution of each pathways to the synaptic plasticity and cognitive effects of estrogen. In closing, whilemuch has been learned in the past several decades concerning estrogen neuroprotective and neurotrophic actions in the brain, significant work lies ahead to fully unravel the complexities of estrogen action in the brain and to fully understand itsmechanisms and implications. Nevertheless, the continued use of multiple species, multiple models/approaches, and the strategy of employing technological advances as they become available should continue to speed progress in this exciting area of research and propel the field toward providing answers to many of the key questions that remain.