Animal models of invasive fungal infections have been developed and are applied in a huge number of different animal species for a number of research purposes, for example, the study of pathogenesis, defense mechanisms, and therapeutic strategies. From the different models, which in most cases are based on the same fungal species and often the same strain, as in spontaneous human infections, fundamental results and knowledge of the diagnosis, progression, prophylaxis, and therapy have been achieved. However, in all models, one should be critical with respect to mimicking the disease entity of humans, which is often the focus of the research. In many of the models for instance, the time course is different to the one of humans, and in others, the propensity for localization and containment in specific organs does not parallel the situation in humans. Nevertheless, many animal models of invasive mycoses have proven valuable in a number of research areas. With regard to new generations of anti-mycotic drugs, the models play an essential role in demonstrating antifungal activity, as well as in demonstrating the absence of toxic side effects, a critical step which cannot be accomplished by in vitro studies.