There are important gaps in our understanding of the global burden and transmission dynamics of pandemic influenza. Based on retrospective analysis of a variety of historical datasets illustrating our experience with the 1889, 1918, 1957, 1968 and 2009 pandemics in the Americas, Europe, Africa and Asia, I will discuss how influenza severity and transmission dynamics vary with seasonality, socio-economic conditions, human mobility, and co-circulation of other pathogens.