Throughout history, global influenza outbreaks have sickened large numbers of people, caused many deaths, and disrupted social and economic relations. This article discussed one of the most significant influenza epidemics in America, the Spanish flu (influenza pandemic) from 1918-1919. This epidemic had a tremendous impact on American cities altering the warfare plans of World War I, making close to 1 billion people ill, and killing from 21 to 40 million people. Understanding the extent of the outbreak and the effectiveness of containment measures was overshadowed by the quickness of the disease and the inadequacies of the health reporting system. A review of this catastrophic event was a scenario of greatest concern to medical, public health, and political leaders in charge of developing a response to bioterrorism. The issues that came about during the Spanish flu outbreak offer several lessons on how the suffering and social disruption caused by a large-scale epidemic could be reduced. Five recommendations are presented for an effective medical and public health response to a bioterrorist attack and to plan for a large-scale infectious disease emergency: (1) build capacity to care for mass casualties; (2) respect social mores relating to burial practices; (3) characterize outbreak accurately and promptly; (4) earn public confidence in emergency measures; and (5) guard against discrimination and allocate resources fairly. Medical, public health, and policy communities need to be acutely aware of the potential frailty of populations and institutions when faced with an infectious disease emergency, especially a deliberate act. References