Recent work suggests that fungal virulence factors important in human disease have evolved through interactions with environmental predators such as amoebae, nematodes, and insects. This has allowed the use of simple model hosts for the study of fungal pathogenesis; specifically, the nematode Caenorhabditis elegans has become a model host to study medically important fungi. Alternative model hosts can be used as easy tools to identify virulence factors of pathogens, to study evolutionarily preserved immune responses, and to identify novel antifungal compounds with low cost. This chapter describes assays utilizing the nematode in studies on fungal-host interactions and antifungal drug discovery. These assays include the nematode killing assay, the progeny permissive assay, and antifungal compound discovery assay.