The United States currently has an emergency supply of smallpox vaccine.

There is no proven treatment for smallpox but research to evaluate new antiviral agents is ongoing. Patients with smallpox can benefit from supportive therapy (intravenous fluids, medicine to control fever or pain, etc.) and antibiotics for any secondary bacterial infections that occur.

The incubation period for smallpox is 8 to 17 days, with people usually getting sick 10 to 12 days after infection. Symptoms start with malaise, fever, rigors, vomiting, headache, and backache. The trademark smallpox rash appears after two to four days, first on the face and arms and later on the legs, quickly progressing to red spots, called papules and eventually to large blisters, called pustular vesicles, which are more abundant on the arms and face. Although full-blown smallpox is unique and easy to identify, earlier stages of the rash could be mistaken for chickenpox. When fatal, death occurs within the first or second week of the illness.

Several years ago, Ken Alibek, a former deputy director of the Soviet Union's civilian bioweapons program, indicated that the former Soviet government had developed a program to produce smallpox virus in large quantities and adapt it for use in bombs and intercontinental ballistic missiles.

By international agreement, the main stores of smallpox virus from the Cold War superpowers are kept securely at the CDC's headquarters in Atlanta and at a similar institute in Moscow.