Although the strategies of reproduction vary widely between species, all share a common goal: the production of offspring. Unfortunately, the importance of reproduction does not guarantee its success, and there is thus great interest in better understanding this process so it can be optimized to ensure a positive outcome. The fruit fly Drosophila melanogaster is an excellent system with which to study the molecular events underpinning successful reproduction-particularly, non-sperm components of the male ejaculate such as seminal fluid proteins. One important seminal fluid protein is Sex Peptide, which elicits many postmating responses in the mated female. Most of Sex Peptide’s action requires that it bind to sperm within the mated female and then have its active region cleaved from sperm. The work described in this thesis takes a multipronged approach to identify molecules and mechanisms that mediate these crucial processes. A genetic screen of novel sperm-bound seminal fluid proteins has identified promising candidates that may be involved in Sex Peptide binding to sperm. Transgenic flies carrying tagged Sex Peptide constructs are nearly built for a proteomic screen of Sex Peptide interacting partners. Additionally, ColabFold modeling of Sex Peptide against various proteomes of interest, such as sperm and seminal fluid proteins, returned a potentially direct interaction between a dimer of CG17575, a member of the seminal fluid protein network known to bind Sex Peptide to sperm, and Sex Peptide itself-as well as CG9997. Overall, these findings emphasize that seminal fluid proteins elicit multifaceted responses in the mated female through networks of complex interactions.