This review will focus on the “non-reproductive” effects of estrogen in the brain, specifically on the neuroprotective
and neurotrophic/synaptic plasticity actions of estrogen. Much of the work in these areas has been conducted in rodent animal models; however, there is a growing body ofwork in humans and non-human primates, which will also be presented and discussed in context with the findings in rodents. There is also a small but growing literature on estrogen analogues, such as the clinically relevant selective estrogen receptor modulators (SERMs), and their effects on brain plasticity and neuroprotection, which will also be discussed. A major goal of the review is to discuss potential sites and mechanisms of action for estrogen in the modulation of plasticity, cognition and neuroprotection, and project possible future directions for these important fields of research. An additional goal is to discuss current controversies in the field, and propose potential future directions for research.