Aspergillosis is an airborne fungal disease caused by Aspergillus spp., a group of ubiquitous molds. This disease causes high morbidity and mortality in both humans and animals. The growing importance of this infection over recent decades has created a need for practical and reproducible models of aspergillosis. The use of laboratory animals provides a platform to understand fungal virulence and pathophysiology, assess diagnostic tools, and evaluate new antifungal drugs. In this review, we describe the fungus, various Aspergillus-related diseases in humans and animals and various experimental animal models. Overall, we highlight the advantages and limitations of the animal models, the experimental variables that can affect the course of the disease and the reproducibility of infection, and the critical need for standardization of the species, immunosuppressive drugs, route of infection, and diagnostic criteria to use.