Among the medical texts in early American physician Benjamin Rush’s library was a copy of Daniel Defoe’s 1722 novel A Journal of the Plague Year. Three years before his own encounter with a devastating 1793 yellow fever outbreak in Philadelphia, Rush penned in the volume, “For the instruction, & entertainment I have received from this book, I am truly thankful.”1 Rush underlined and marked key passages as well, including one about a physician combating disease with garlic, tobacco, and vinegar, and compiled an index including entries like “Origin of the plague,” “State of morals after the plague,” “The number who died of the plague & in what months,” and “Effects of terror.” Gleaning medical and social information about disease from this fictionalized account, Rush demonstrates how tightly literary and medical knowledge were intertwined in the early United States.