We conducted a systematic review of the scientific literature from 1966 to 2005 to determine whether animals could provide early warning of a bioterrorism attack, serve as markers for ongoing exposure risk, and amplify or propagate a bioterrorism outbreak. We found evidence that, for certain bioterrorism agents, pets, wildlife, or livestock could provide early warning and that for other agents, humans would likely manifest symptoms before illness could be detected in animals. After an acute attack, active surveillance of wild or domestic animal populations could help identify many ongoing exposure risks. If certain bioterrorism agents found their way into animal populations, they could spread widely through animal-to-animal transmission and prove difficult to control. The public health infrastructure must look beyond passive surveillance of acute animal disease events to build capacity for active surveillance and intervention efforts to detect and control ongoing outbreaks of disease in domestic and wild animal populations.