The female brain is highly dynamic and can fundamentally remodel throughout the normal ovarian cycle as well as in critical life stages including perinatal development, pregnancy and old-age. As such, females are particularly vulnerable to infections, psychological disorders, certain cancers, and cognitive impairments. We will present the latest evidence on the female brain; how it develops through the neonatal period; how it changes through the ovarian cycle in normal individuals; how it adapts to pregnancy and postpartum; how it responds to illness and disease, particularly cancer; and, finally, how it is shaped by old age. Throughout, we will highlight female vulnerability to and resilience against disease and dysfunction in the face of environmental challenges.