Sex determination is the commitment of an organism toward male or female development. Traditionally, in mammals, sex determination is considered equivalent to gonadal determination. Since the presence or the absence of the testes ultimately determines the phenotype of the external genitalia, sex determination is typically seen as equivalent to testis determination. But what exactly does sex determine? The endpoint of sex determination is almost invariably seen as the reproductive structures, which represent the most obvious phenotypic difference between the sexes. One could argue that the most striking differences between males and females are not the anatomy of the genitals, but the size of the gametes-considerably larger in females than males. In fact, there could be many different endpoints to sex determination, leading to differences between the sexes: brain sexual differences, behavioral differences, and susceptibility to disease. The central dogma of sexual differentiation, stemming initially from the gonad-transfer experiments of Alfred Jost, is that sexual dimorphisms of all somatic tissues are dependent on the testicular secretion of the developing fetus. In this chapter, we will take the example of sex differences in brain and behavior as an endpoint of sex determination. We will argue that genetic factors play a role in sexually dimorphic traits such as the number of dopaminergic cells in the mesencephalon, aggression, and sexual orientation, independently from gonadal hormones.