The United States has made considerable progress in pandemic preparedness. Limited attention, however, has been given to the challenges faced by populations that will be at increased risk of the consequences of the pandemic, including challenges caused by societal, economic, and health-related factors. This supplement to the American Journal of Public Health focuses on the challenges faced by at-risk and vulnerable populations in preparing for and responding to an influenza pandemic. Here, we provide background information for subsequent articles throughout the supplement. We summarize (1) seasonal influenza epidemiology, transmission, clinical illness, diagnosis, vaccines, and antiviral medications; (2) H5N1 avian influenza; and (3) pandemic influenza vaccines, antiviral medications, and nonpharmaceutical interventions.