Because influenza infections can present with a wide range of nonspecific clinical signs and symptoms and can be responsible for numerous complications, emergency clinicians must be keenly alert for this possible diagnosis. A knowledge of the local seasonal prevalence of influenza as well as the specific strains circulating within a particular region are crucial for appropriate diagnostic and treatment decisions and will help to limit useless testing when empiric therapy would be more appropriate. Such considerations will improve efficiency in the ED while still ensuring that patients who are at increased risk for a more severe disease course will receive timely and appropriate therapy. With the evolution of new influenza strains through genetic reassortment combined with the globalization of disease, the world is at greater risk than ever before for pandemics. Today’s emergency clinician must be both an epidemiologist and a clinician in order to recognize emerging pathogens and make the complex decisions required for individual and community health.