Although mice have been used for fifty years to model human disease, it has become apparent that results generated in mouse models reflect human disease quite poorly, particularly for diseases with an inflammatory component. Large litter sizes, short gestation times, and contaminated habitats have favored the evolution of rodents that are highly resistant to most inflammatory challenges relative to humans. For example, mice are a million-fold more resistant to a common bacterial toxin—endotoxin—than humans. For unclear reasons, certain other vertebrate species, including some primates, also evolved high natural resistance to inflammation. This variation in inflammatory sensitivity between species and the failure of models to adequately mimic human disease are a major problem for biomedical research and drug development. As a direct effect, there are costly errors and inefficiencies in the way that research is performed and drugs are developed. To evaluate this problem, a diverse group of experts in theoretical biology, primatology, evolutionary science, genetics, computational biology, immunology, and drug development are gathering to discuss the concept that—instead of trying to force artificially the two species to be similar (as is currently done with the use of mouse models)—a better and more specific understanding of species’ differences could help interpret current models and may actually be taken advantage of to develop new therapies.