A central goal in ecology and evolution is to explain the mechanisms that determine the fitness of species. In the context of infectious disease epidemiology, understanding pathogen fitness informs approaches to disease management, especially in the case of rapidly evolving pathogens such as seasonal influenza. This dissertation examines how human ecology shapes the ecology and evolution of seasonal influenza, and thereby affects the fitness of influenza viruses. We examine how human ecology shapes geographical patterns of influenza’s evolution. We them examine how public health interventions through vaccination may affect long term patterns of evolution. We find that vaccination can slow the evolution of rapidly-evolving pathogens, which potentially reduces disease burden by more than is appreciated using present models. However, we do not find consistent evidence for vaccine-driven selection in presently available surveillance data.