Influenza viruses are emerging and re-emerging viruses that cause worldwide epidemics and pandemics. Despite substantial knowledge of the mechanisms of infection and immunity, only modest progress has been made in human influenza vaccine development. The rational basis for influenza vaccine development originates in animal models that have helped us to understand influenza species barriers, virus-host interactions, factors that affect transmission, disease pathogenesis, and disease intervention strategies. As influenza evolution can surmount species barriers and disease intervention strategies that include vaccines, our need for appropriate animal models and potentially new host species will evolve to meet these adaptive challenges. This chapter discusses animal models for evaluating vaccines and discusses the challenges and strengths of these models.