Public health investigators have successfully carried out epidemiologic investigations of outbreaks of disease for many years. By far the majority of these outbreaks have occurred naturally. With the recent illnesses resulting from deliberate dissemination of B. anthracis on an unsuspecting population, public health investigation of diseases must now include consideration of bioterrorism as a potential cause of outbreaks of disease. The features of naturally occurring outbreaks have a certain amount of predictability in terms of consistency with previous occurrences, or at least biological plausibility. However, with a deliberately introduced outbreak or infection among a population, this predictability is minimized. In this paper, the authors propose some epidemiologic clues that highlight features of outbreaks that may be suggestive of bioterrorism. They also describe briefly the general process of involvement of agencies at various levels of government, public health and non-public health, depending on the extent of an outbreak or level of suspicion.