This chapter will describe pandemic threats and the steps necessary to reduce morbidity and mortality. An explanation is provided on genetic mutations leading to the emergence of novel influenza strains. Medical countermeasures include vaccination and antiviral medications. Public messaging is also important to promote flu shots, reinforce basic hygiene measures, and instruct those who may be ill to limit contacts. The World Health Organization (WHO) tracks seasonal influenza for anomalies indicating an emerging pandemic influenza strain. WHO updated the international pandemic alert system after the 2009–2010 H1N1 pandemic. With each declaration, temporary recommendations are provided, and added regulatory actions are taken by WHO member states. In addition, the Centers for Disease Control and Prevention (CDC) updated the U.S. framework for pandemic influenza preparedness and response. Each pandemic interval is accompanied by specific recommendations for state and local public health authorities. Effective influenza control includes both pharmaceutical and nonpharmaceutical recommendations. Other severe viral pandemic respiratory threats, including the “Middle East Respiratory Syndrome Coronavirus” (MERS-CoV), require similar resources and infrastructure to manage.