A 17-year-long saga ended in July with the first approval of a drug for treating smallpox infections. Long sought after, but particularly so after the anthrax attacks in 2011, a small-molecule inhibitor of virus extrusion from cells, Tpoxx (tecovirimat), was approved by the FDA in July, after the agency's Antimicrobial Drugs Advisory Committee voted unanimously for approval in May. SIGA Technologies of New York took the molecule through clinical trials, after they showed in 2005 that it protected mice from lethal infections with a related poxvirus. (J. Virol. 79, 13139–13148). The FDA based its decision on results from mice, enabled by the 'animal rule', which kicks in when human studies are unethical. In a pivotal trial, 380 healthy people were dosed for 14 days with no severe adverse events, as reported in June (N. Engl. J. Med. 379, 44–53, 2018). The government had been seeking a treatment for smallpox for decades. Vaccination programs for smallpox ended around 1979, when the virus was deemed eradicated. Hence, people below a certain age are susceptible to infection by smallpox, considered a category A bioterror agent. Although there are millions of doses of a vaccine stockpiled in the event of an infection, it cannot be given to immune-compromised people and sufferers of some skin disorders. Although all known stocks of the virus were believed to be accounted for, in 2014 researchers at the NIH discovered vials of smallpox in the institute's basement. Finally, the recent synthesis of a poxvirus from scratch has people worried that smallpox, natural or synthetic, might someday find its way into the public sphere. Tpoxx development began at the now defunct ViroPharma in collaboration with the US Army Medical Research Institute of Infectious Diseases, SIGA, and others. After the preclinical work and early safety trials, the US government ordered 1.2 million doses for the Strategic National Stockpile, garnering SIGA $500 million. Now, with the approval, SIGA will get the first Material Threat Medical Countermeasure Priority Review voucher, which could be worth many millions more.