At present, there is the highest number of displaced persons since World War II. Add to that the approximately one billion people living in so-designated fragile states, as well as multiple large-scale humanitarian crises. These vulnerable populations are subject direct and indirect health effects. Unfortunately, delivering effective interventions to them is fraught with difficulty, and the evidence base is weak. The chapter examines the conditions that give rise to acute and prevalent health risks among vulnerable populations, and the present challenges to research. These issues are particularly pertinent to inform our understanding of the ecology of infectious disease. Research contributions are also essential to address infectious diseases and to weigh the relative benefits and risks of different control options. Effective research in crises provides critical information for our understanding of infections among the most vulnerable.