Smallpox is a highly contagious disease characterized by fever, rash, and a high mortality rate, known as smallpox in ancient and modern times. Smallpox virus is an orthopoxvirus in the family Poxviridae. Other poxviruses that infect humans include molluscum contagiosum, vaccinia (the virus used in the smallpox vaccine), and monkeypox. There are two forms of smallpox: variola major and variola minor, the former being a serious disease and the latter a milder infection. In 1979, global eradication of smallpox was declared, and several factors contributed to the eradication effort: humans are the only known reservoir of the virus, there is no asymptomatic carrier state, there is an effective vaccine, and vaccination of contacts resulted in prevention or modification of the disease. Nonspecific laboratory findings include granulocytopenia, thrombocytopenia, and lymphopenia, which are common in the prodromal phase and early in the rash. Leukopenia often occurs when blisters become pustules. Disseminated intravascular coagulation is often seen in patients with hemorrhagic smallpox. Complications of smallpox include secondary bacterial infections of the skin, keratitis and corneal ulcers leading to blindness, viral arthritis and osteomyelitis, bacterial pneumonia, cholecystitis, encephalitis, and residual paresthesias that appear hypopigmented in darker-skinned individuals and hyperpigmented in lighter-skinned patients.