Understanding development is relevant to understanding evolution because developmental processes structure the expression of phenotypic variation upon which natural selection acts. Advances in developmental biology are fueling a new synthesis of developmental and evolutionary biology, but it remains unclear how to use developmental information that largely derives from a few model organisms to test hypotheses about the evolutionary developmental biology of taxa such as humans and other primates that have not been or are not amenable to direct study through experimental developmental biology. In this article, we discuss how and when model organisms like mice are useful for studying the evolutionary developmental biology of even rather distantly related and morphologically different groups like primates. A productive approach is to focus on processes that are likely to play key roles in producing evolutionarily significant phenotypic variation across a large phylogenetic range. We illustrate this approach by applying the analysis of craniofacial variation in mouse mutant models to primate and human evolution.