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Epidemic disease plays a central role in the development of human societies, through a symbiotic relationship that predates the development of agriculture. Many historians have explored how epidemics have shaped human history demographically, culturally, politically, and financially. However, less research has explored how the underlying biology of epidemic disease has shaped the experience of childhood. This paper will explore how the biology of epidemics such as the bubonic plague, cholera, and more recently, HIV, have manifested in the culture of childhood play. It will focus particularly on sources that help us understand how children processed the morbidity of such diseases through childhood play, including games, books, and nursery rhymes.