Smallpox, once a major menace of humankind, is the only endemic anthroponosis that has completely disappeared due to organized human action. The history of variola and of the rationales of prevention and control associated with ancient variolation, modern vaccination and the surrounding research enterprises and sanitary regimes provide paradigmatic examples of the involvement of medical thought and scientific dynamics with natural and cultural necessities and technological evolution. Taking the form of a broad historiographic sketch this is discussed not only based on representative literature, but contemplating material relics of the medical endeavor with smallpox. The objects are maintained by the Austrian Federal Museum of Pathological Anatomy, located in the unique historic building known as Narrenturm or Fool's Tower in Vienna's traditional medical district. They range from textual documents to wet specimens recently reactivated for virological research. Special focus lies on waxen moulages, crafted in the context of early 20th century clinical research and teaching.