Despite its eradication, smallpox remains a subject of concern due to its potential use as a bioweapon. The variola virus is classified as a Category A bioterrorism agent, prompting ongoing research to improve preparedness and response strategies. Stockpiles of the smallpox vaccine are maintained for emergency use, and research explores novel antiviral treatments and vaccination approaches. The legacy of smallpox research extends beyond eradication efforts. The study of the variola virus and related poxviruses contributes to our understanding of viral pathogenesis, immunology, and vaccine development. Poxvirus research has implications for broader vaccine design and antiviral strategies against related pathogens. Post-eradication challenges include the secure handling and storage of remaining variola virus stocks, located in designated repositories in the United States and Russia. The debate over the destruction of these stocks continues, weighing concerns about accidental release or deliberate misuse against the benefits of retaining the virus for research purposes.