Gareth Williams, former Dean of Medicine at Bristol University, provides a compelling and timely account of humanity’s battle against one of its greatest killers. He traces the dramatic rise and fall of smallpox, including the creation of the world’s first vaccine by Edward Jenner, which ultimately led to the disease’s eradication in 1980—a turning point in the history of smallpox, and arguably the greatest achievement of preventative medicine. The saga of smallpox still resonates today, with its legacies including the anti-vaccination movement, and more recently, the nightmarish possibility that a virus resembling smallpox could return, either through natural evolution—as in the case of monkeypox—or built from scratch in a bioterrorist’s laboratory. Given its greater infectivity and mortality, such a virus could lead to a much more devastating pandemic than COVID–19.