Purpose of Review <p>Fungal pathogens represent a serious cause of disease and death in immunodeficient and immunocompromised patients. The increasing incidence of antifungal drug resistance poses an elevated risk for susceptible patients. A variety of model systems can be used to study fungal - host interactions and may facilitate improved diagnosis and the development of more effective therapies.</p> Recent Findings <p>A wide variety of in vivo and in vitro model systems is now used for studying different aspects of human fungal pathogens. Mammalian models such as mice, rabbits and guinea pigs have been used and provided interesting insights into the immune response to fungal infection. Cell systems have utilized epithelial and endothelial cells as well as cultured cell lines to study fungal – cell interactions. More complex 2D and 3D models systems such as organ on a chip and organoids offer more realistic environments for studying fungal – host interactions. Zebra fish embryos have recently been utilized and can offer insights into in vivo efficacy of antifungal therapies. Invertebrate models include the use of nematodes and a number of insect species (e.g. <i>Drosophila melanogaster</i>, <i>Galleria mellonella</i>) can provide a means to rapidly study aspects of fungal virulence and to measure the in vivo toxicity and efficacy of antifungal drugs.</p> Summary <p>A range of in vivo and in vitro model systems is now widely used in research. In vitro cell systems and the use of insects or nematodes offer a means to rapidly assess fungal virulence or the efficacy of antifungal therapies before embarking on more costly, and ethically restricted, mammalian testing.</p>