Natural product-based drug discovery has been deemphasized by the pharmaceutical industry. This situation is discordant with the fact that most people in developing countries rely on traditional medicines derived from local biodiversity for healthcare. Despite economic growth in the past 10 years, Africa remains plagued by parasitic infections, out of reach of eradication. Limited regional funding for drug discovery complicates the situation. Novel models are needed to bring sustainability to local drug discovery programs. This Opinion describes an innovative partnership that promotes local leadership to harness a recombinant yeast-based assay to screen for novel anthelmintic candidates in collections of African natural products. Implementation of this strategy in biodiversity-rich but resource-constrained settings can help build sustainable local capacity for drug discovery.