Living organisms compete for survival and reproduction, whereupon the fittest live and thrive and the weakest fail and some cases even die. This battle for life acts on different levels, causing individuals of distinct species as well as individuals of the same species to compete over a variety of limiting resources such as food, breeding sites and mates. An important form of competition is driven by sexual conflict and often occurs when reproductive strategies between males and female diverge. These occur because there are differences in the evolutionary interests of the sexes over, for example, optimal reproductive rate, gamete size and parental investments. This has led to the evolution of different strategies to alter or overcome the manipulation of one sex by other, while maintaining a base line level of cooperation sufficient to ensure successful reproduction. This sexual conflict is an important evolutionary process as it can drive rapid evolutionary change. The manipulation of one sex by the other through molecular interactions has been illuminated in studies using the fruit fly Drosophila melanogaster. Males tend to maximize their chances at fatherhood by releasing both sperm and semen inside the female’s body during mating. The effects of semen proteins can benefit both sperm and eggs, but intriguingly they can also favour the interests of males whilst generating costs in females, resulting in sexual conflict. In Drosophila melanogaster, the female body has been the battlefield of sexual conflict, as semen proteins exert their effects in females after mating. This manipulation by males through molecular interactions can inflict substantial physical and physiological costs of mating in females. One enigmatic seminal fluid protein the ‘Sex Peptide’, generates strikingly diverse changes in female physiological and reproductive behaviour. Sex Peptide triggers remarkable female post mating responses including altered fertility, immunity, libido, eating and sleep patterns, by the activation of diverse sets of genes. In many studies of the molecular mechanisms of female manipulation via the effects of Sex Peptide, genetic variation is minimised in order to clearly delineate biological functions. However, to understand the evolutionary processes and dynamics that characterise Sex Peptide mediated interactions between males and females, it is important to study this genetic variation. With high-throughput sequencing technologies that have provided resources such as >200 fully sequenced DGRP lines (Drosophila Genome Reference Panel), we traced the impact of the enigmatic Sex Peptide on the fruitfly genome. In this thesis I performed an in-depth investigation of the phenotypic and genomic differences among 30-32 DGRP lines, with respect to male release of, and female responses to, Sex Peptide. I measured phenotypic variation for Sex Peptide release in males; and in females the phenotypic variation in immune responses, egg laying, receptivity and longevity in response to Sex Peptide receipt. I compared these phenotypic post-mating responses to those of females that mated to males with a null-allele for Sex Peptide, to distinguish the specific response to Sex Pepetide. I mapped these phenotypes to genomic variation using Genome Wide Association Studies and conducted functional characterizations on the genomic variation identified