Few catastrophes can compare with the global impact of a severe influenza pandemic. The 1918-1919 pandemic was associated with more than 500,000 deaths in the USA and an estimated 20-40 million deaths worldwide, though some place the global total much higher. In an era when infectious disease mortality had been steadily decreasing, the 1918-1919 pandemic caused a large spike in overall population mortality, temporarily reversing decades of progress. The US Department of Health and Human Services, extrapolating from the 1918-1919 pandemic to the current US population size and demographics, has estimated that a comparable pandemic today would result in almost two million deaths. Vaccination is an important component of a pandemic response. Public health measures such as reduction of close contacts with others, improved hygiene, and respiratory protection with facemasks or respirators can reduce the risk of exposure and illness (Germann et al. 2006; Ferguson et al. 2006), but would not reduce susceptibility among the population. Prophylaxis with antiviral medications also may prevent illness but depends on the availability of large antiviral drug stockpiles and also does not provide long-term immunity. By contrast, immunization with a well-matched pandemic vaccine would provide active immunity and represent the most durable pandemic response. However, given current timelines for the development of a pandemic influenza vaccine and its production capacity, vaccine is likely not to be available in sufficient quantities to protect the entire population before pandemic outbreaks occur, and thus potentially limited stocks may need to be prioritized. This chapter reviews information on influenza vaccine production capacity, describes approaches used in the USA to set priorities for vaccination in the setting of limited supply, and presents a proposed strategy for prioritization.