This inquiry is framed by the compelling question “Can disease change the world?” Among the many catastrophic global pandemics in history, perhaps none achieved the notoriety of the Black Death. The Black Death was a massive outbreak of the bubonic plague caused by infectious bacteria. Thought by scientists to have been spread by contaminated fleas on rats and/or other rodents, the Black Death quickly decimated entire families and communities. In doing so, the Black Death led more than one observer of the time to ponder whether the apocalypse had begun. The Black Death began and first spread on the Silk Roads through central Asia in the early 14th century, and by mid-century moved via merchant ships into North Africa and Europe, where it would kill nearly one-half of the population. It took almost 150 years for Europe’s population to recover. By investigating the compelling question “Can disease change the world?” students consider the causes, symptoms, and reasons for the rapid geographic expansion of the disease and how this pandemic affected people of the 14th century and beyond. Through their investigation of sources in this inquiry, students should develop an understanding of the consequences of the Black Death and an informed awareness of the importance of preparing for future diseases and possible pandemics.