Meiosis ordinarily ensures the fair segregation of alleles to gametes. Meiotic drivers are selfish genetic elements that subvert this normally fair process and bias their transmission to the next generation, violating the principles of Mendelian inheritance. Drivers are pervasive in sexually reproducing organisms and can spread in populations, even when they harm the host. We know little about the molecular mechanisms of drive but themes emerging from studies of sperm-killing male meiotic drivers implicate chromatin regulation and small RNAs as important factors. I study the molecular mechanism of drive in a powerful model system: Segregation Distorter (SD), a sperm killer found in natural populations of Drosophila melanogaster. SD causes sperm dysfunction by inducing a chromatin defect in wild type spermatids containing a sensitive allele of its target—a large block of tandem satellite DNA repeats called Responder (Rsp)—through an unknown mechanism. We aim to understand the molecular basis of the SD-induced sperm chromatin defect and the role of the target in drive sensitivity. My research focuses on two complementary goals: 1) to determine the role of Rsp satellite-derived RNA in the mechanism of SD; and 2) to determine the timing and nature of the chromatin phenotype associated with sperm dysfunction. We use techniques for manipulating Rsp satellite-derived RNA, with genetic and cytological approaches to quantify their effects on drive strength and chromatin phenotypes. To study the chromatin defect in detail and pinpoint its timing, we use long-read-based epigenomic assays to study the dynamics of histone marks in driving testes and their controls. This work sheds light on mechanisms of drive, dynamic changes in chromatin states in testes, and how satellite DNAs are regulated in the male germline. These insights have broad implications for our understanding of factors influencing male fertility in general and how spermatogenesis is vulnerable to selfish genetic elements.