Estrogen acting through two estrogen receptors (ERs), ERalpha and ERbeta, regulates multiple functions in the central nervous system. Studies in rodent brains have revealed that ERalpha is the predominant ER in the hypothalamus and controls reproduction. ERbeta influences on non-reproductive processes and appears to be the main ER subtype expressed in the cerebral cortex, the hippocampus, the cerebellum and the dorsal raphe. During embryogenesis, estrogen plays an important role in brain development regulating maturation of distinct brain structures, thereby contributing to modulation of the function of these structures. Studies on the brains of ERbeta knockout mice revealed that, during embryonic brain development, ERbeta affects cortical layering and interneuron migration, thus playing a key role in brain morphogenesis. This chapter will focus on the roles of ERbeta in several aspects of the development and function of the mammalian central nervous system.