Although smallpox was globally eradicated in 1977, the current threat of smallpox as a bioterrorism agent is unknown. Based on intelligence reports, the U. S. government and public health sectors have recommended smallpox vaccination for very select individuals. Patients with cancer are at particular risk for complications from the smallpox vaccine because of potential immunosuppression. Vaccinated nurses caring for these patients also need to take special precautions because of the possibility of secondary transmission of this live vaccine to patients. This article reviews background information on bioterrorism, the presentation and clinical features of smallpox, contraindications to the smallpox vaccine, and implications for oncology nurses.