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The ongoing COVID-19 pandemic has justifiably captured the attention of people around the world since late 2019. It has produced in many people a new perspective on or, indeed, a new realization about our potential vulnerability to emerging infectious diseases. However, our species has experienced numerous catastrophic disease pandemics in the past, and in addition to concerns about the harm being produced during the pandemic and the potential long-term sequelae of the disease, what has been frustrating for many public health experts, anthropologists, and historians is awareness that many of the outcomes of COVID-19 are not inevitable and might have been preventable had we actually heeded lessons from the past. We are currently witnessing variation in exposure risk, symptoms, and mortality from COVID-19, but these patterns are not surprising given what we know about past pandemics. We review here the literature on the demographic and evolutionary consequences of the Second Pandemic of Plague (ca. fourteenth–nineteenth centuries C.E.) and the 1918 influenza pandemic, two of the most devastating pandemics in recorded human history. These both provide case studies of the ways in which sociocultural and environmental contexts shape the experiences and outcomes of pandemic disease. Many of the factors at work during these past pandemics continue to be reproduced in modern contexts, and ultimately our hope is that by highlighting the outcomes that are at least theoretically preventable, we can leverage our knowledge about past experiences to prepare for and respond to disease today.