Sex differences in the nervous system are prevalent throughout the animal kingdom. In humans, the corpus callosum and anterior commissure are larger in females, whereas some hypothalamic nuclei and associated structures are larger in males. Numerous studies in rodents have demonstrated that when these nuclei are exposed to circulating androgens during the critical period around birth, they develop into male-typical structures. In addition to this organizational effect, androgens exert an activational effect during adulthood. For example, sexually dimorphic gene expression in the hypothalamus and amygdala depends on circulating androgen levels. Cckar encodes a G protein-coupled receptor and its expression is sexually dimorphic. The major of Cckar-expressing neurons in the ventrolateral division of ventromedial hypothalamus (VMHvl) also express progesterone receptor (PR), with a female-biased expansion of arborizations in the anteroventral periventricular hypothalamic nucleus. Selective ablation of these PR-positive neurons in the VMHvl results in a marked reduction in female sexual receptivity and male aggression, demonstrating that these sexually dimorphic neurons contribute to gendered behavior in mammals. Remarkable sex differences in single neurons have been documented in the fruitfly (Drosophila melanogaster). The fruitless (fru) gene in the fruitfly is considered as a major regulator of male courtship circuitry; a male specific fru-expressing neuron cluster, P1, can initiate male courtship when artificially activated even in the absence of courtship target (e.g., a female). The fru gene encodes a set of putative transcription factors that appear to orchestrate the transcription of ~100 genes by recruiting chromatin regulators, histone deacetylase 1 or heterochromatin protein 1a, to the target sites. These studies have unraveled the causal link among genes, brain sexual dimorphisms and gendered behaviors.