This study investigates genes enriched for expression in the spermatheca, the long-term sperm storage organ (SSO) of female Drosophila. SSO genes are likely to play an important role in processes of sexual selection such as sperm competition and cryptic female choice. Although there is keen interest in the mechanisms of sexual selection at the molecular level, very little is known about the female genes that are involved. In the present study, a high proportion of genes enriched for expression in the spermatheca are evolving rapidly. Most of the rapidly evolving genes are proteases and genes of unknown function that could play a specialized role in the spermatheca. A high percentage of the rapidly evolving genes have secretion signals and thus could encode proteins that directly interact with ejaculate proteins and coevolve with them. In addition to identifying rapidly evolving genes, the present study documents categories of genes that could play a role in spermatheca function such as storing, maintaining, and utilizing sperm. In general, candidate genes discovered in this study could play a key role in sperm competition, cryptic female choice of sperm, and sexually antagonistic coevolution, and ultimately speciation.