Females produce eggs and males produce sperm. Work in Drosophila is helping to elucidate how this sex-specific germline differentiation is genetically encoded. While important details remain somewhat controversial, it is clear that signals generated by somatic cells, probably in the embryonic gonads, are required as extrinsic factors for germline sex determination. It is equally clear that the sex chromosome karyotype of the germ cell is an intrinsic factor for germline sex determination. There is also extensive somatic signaling required for differentiation of germline cells in the adult gonads. Mismatched germline and somatic line sexual identities place germ cells in an inappropriate signaling milieu, which results in either failed maintenance of germline stems cells when female germ cells are in a male soma or overproliferation of germline cells when male germ cells are in a female soma. The well-studied somatic sex determination genes including transformer, transformer-2, and doublesex are clearly involved in the nonautonomous signaling from somatic cells, while the autonomous functions of genes including ovo, ovarian tumor, and Sex-lethal are involved in the germline. The integration of these two pathways is not yet clear.