The role of estrogen during brain development is well documented. Estrogen influences cell survival and differentiation and also controls the formation and maintenance of neural networks. Knowledge of trophic estrogen action in the central nervous system (CNS) was the basis for the establishment of research programs directed toward a potential function of estrogen as a neuroprotective factor in the adult brain. Considerable evidence has accumulated over the years supporting this hypothesis. Experimental and epidemiologic studies as well as clinical trials have demonstrated that estrogen is beneficial for the course of neurodegenerative disorders such as Parkinson and Alzheimer diseases but may also protect neurons from postischemic neuronal degeneration. In this article, we aim to unravel potential physiologic responses and cell survival strategies that allow a more detailed understanding of estrogen-mediated neuroprotection in the brain. In particular, we focus on the participation of estrogen in the regulation of apoptotic processes. Furthermore, we present data on reciprocal estrogen-growth factor interactions. Both of these mechanisms were found to operate during brain development and to conciliate estrogen effects on neurons. This makes them likely candidates for taking part in conveying estrogen-dependent neuroprotection in the adult CNS.