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What are the immunological facets of a highly successful viral epidemic, and what are likely successful strategies that can be used to counter its spread? Unlike many challenges in biology and public policy, viral epidemics are unique in that they require swift response, and quick application of existing knowledge to infer the underlying biology of a new pathological agent. This essay contextualizes the experience and findings from the viral immunology literature to respond to a hypothetical (yet likely) emerging viral epidemic. It begins with a review of the causes of some defining features of highly virulent viral epidemics, including causes of mortality, viral virulence, and immune evasion and suppression tactics. We provide an overview of lines of investigation to characterize emerging viral epidemics, including a brief survey of clinical and biological assays for immune surveillance and in-depth interrogation of viral biology. Finally, we provide a broad overview of management and vaccine development response strategies.