Theoretically, human illness could result accidentally in a biological attack aimed at domestic livestock, or as the intended outcome of a bioterrorist utilizing animal species, food, or foodstuffs to specifically target human populations. The number and diversity of agents, modes of transmission, disease ecologies, and illnesses and outcomes form a vast zoonotic and food‐borne disease “threat space” against which we must defend. In this brief resume, we describe the diversity of zoonotic and food‐borne threats and observe that most of these remain poorly characterized from an analytical viewpoint. Options for control exist for many of these diseases, but often the options are problematic. Significant gaps exist in terms of prophylactic and therapeutic agents for the majority of these diseases. Methodologies exist that can be applied to identify and analyze potential public health prevention and response strategies and to guide future research. Although programmatic opportunities exist for pursuing such research, much remains to be done.