Multiple mechanisms mediate the impact of hormones upon brain. Brain functions putatively impacted by hormones fall into categories such as motor mood and cognition. Hormones also have been implicated as hastening protecting or having nil effect upon molecular processes subserving neurodegeneration. Due to insufficient and contradictory findings the debate over the importance of hormones for brain health continues unabated and clinicians and patients alike are left with few solid guidelines. Indeed awareness that the brain is an important target tissue of steroids is still emerging. To complicate matters drugs which modify or alter hormone levels have been added to the clinical armamentarium but rarely has the impact of these hormonal mediators upon the brain been studied at molecular and clinical levels. Hence drugs which modify or interdict hormone action are now in relatively widespread use while belatedly we are trying to understand the neurological psychological behavioral and psychiatric implications. Recently we have focused on the impact of hormones upon brain neurotransmission using state-of-the-art neuroimaging approaches. In parallel we have explored the impact of SERM’s and AI’s upon cognitive measures in women being treated for breast cancer. Both approaches confirm that hormones play a significant role in modifying neural substrates subserving cognition and emotion. In particular it appears that aromatase inhibitors impart a more deleterious impact upon cognition than does tamoxifen in women being treated for early stage breast cancer. Further serotonergic neurotransmission which subserves cognition mood metabolism and vegetative activities such as sleep is modulated by physiological concentrations of estradiol and progesterone in young postmenopausal women. When considered in the context of epidemiological studies and other information about the molecular cellular and physiological functions of hormones one must conclude that future studies that intend to delineate the pros and cons of hormonal modifiers should include the brain as one of the important target tissues. In particular comparative neuroimaging studies are suggested as a means of determining which estrogenic substances might best support the postmenopausal brain.