Although it is well recognized that sex-steroids exert both developmental and activational influences on the brain, the cellular and molecular mechanisms underlying their actions are less well understood. Progress is rapid, however, and this paper reviews recent insights gained through manipulation of sex-steroid receptor genes, identification of phenotypes expressing these receptors and how these proteins may also be activated to regulate transcription by ligand-independent pathways. Advances in our understanding of more rapid actions of sex-steroids and the molecular targets involved are also reviewed, as are new studies describing effects on synaptic plasticity and the recent excitement regarding the neuroprotective effects of oestrogen replacement therapy in Alzheimer's disease.