Synopsis Hamilton and Zuk proposed a good-genes model of sexual selection in which genetic variation can be maintained when females prefer ornaments that indicate resistance to parasites. When trait expression depends on a male's resistance, the co-adaptive cycles between host resistance and parasite virulence provide a mechanism in which genetic variation for fitness is continually renewed. The model made predictions at both the intraspecific and interspecific levels. In the three decades since its publication, these predictions have been theoretically examined in models of varying complexity, and empirically tested across many vertebrate and invertebrate taxa. Despite such prolonged interest, however, it has turned out to be extremely difficult to empirically demonstrate the process described, in part because we have not been able to test the underlying mechanisms that would unequivocally identify how parasites act as mediators of sexual selection. Here, we discuss how the use of high-throughput sequencing datasets available from modern genomic approaches might improve our ability to test this model. We expect that important contributions will come through the ability to identify and quantify the suite of parasites likely to influence the evolution of hosts' resistance, to confidently reconstruct phylogenies of both host and parasite taxa, and, perhaps most exciting, to detect generational cycles of heritable variants in populations of hosts and parasites. Integrative approaches, building on systems undergoing parasite-mediated selection with genomic resources already available, will be particularly useful in moving toward robust tests of this hypothesis. We finish by presenting case studies of well-studied host-parasite relationships that represent promising avenues for future research.