Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people living in some of the most resource-poor communities in the world. Over the last decade, we have established high-throughput, whole-organism phenotypic platforms to facilitate screening of large compound collections against schistosomes. Our goal, using these platforms, is to bring new chemical matter into the schistosome drug discovery pipeline for progression as new PZQ replacements or for use in combination with PZQ. While we have completed >500K individual screens and identified incredibly potent compounds, our progress in translating these promising ex vivo results into in vivo efficacy has been slow. We contend that embedding enabling technologies into our pipeline will not only increase the pace of drug discovery but will also focus (often limited) resources around tractable chemical matter/protein target pairings. Here, using examples derived from ongoing projects, I will present how complementary strategies are being developed and deployed in our laboratory to accelerate the search for novel anti-schistosomals.​