The Drosophila melanogaster germ plasm has become the paradigm for understanding both the assembly of a specific cytoplasmic localization during oogenesis and its function. The posterior ooplasm is necessary and sufficient for the induction of germ cells. For its assembly, localization of gurken mRNA and its translation at the posterior pole of early oogenic stages is essential for establishing the posterior pole of the oocyte. Subsequently, oskar mRNA becomes localized to the posterior pole where its translation leads to the assembly of a functional germ plasm. Many gene products are required for producing the posterior polar plasm, but only oskar, tudor, valois, germcell-less and some noncoding RNAs are required for germ cell formation. A key feature of germ cell formation is the precocious segregation of germ cells, which isolates the primordial germ cells from mRNA turnover, new transcription, and continued cell division. nanos is critical for maintaining the transcription quiescent state and it is required to prevent transcription of Sex-lethal in pole cells. In spite of the large body of information about the formation and function of the Drosophila germ plasm, we still do not know what specifically is required to cause the pole cells to be germ cells. A series of unanswered problems is discussed in this chapter.