Although smallpox was eradicated worldwide by 1980, national security experts remain concerned that it could be used in a deliberate attack. The United States and other governments have given priority to developing and stockpiling vaccines and antivirals to protect their populations from the potential reintroduction of this deadly disease. Public health officials are also concerned about the spread of related zoonotic orthopoxviruses such as monkeypox and cowpox, against which smallpox vaccine provides protection. This report analyzes how medical countermeasures available in the US Strategic National Stockpile will be given priority and used in the event of an intentional or accidental release of smallpox in the United States. (Disaster Med Public Health Preparedness. 2015;9:121-126)