The Spanish influenza pandemic of 1918 was the most intense outbreak of disease in human history. It killed upwards of 50 million people (most in a six-week period) casting a long shadow of fear and mystery: nearly a century later, scientists have been unable to explain why, unlike all other influenza outbreaks, it killed young adults in huge numbers. I will describe how analyses of large numbers of influenza virus genomes are revealing the pathway traveled by the genes of this virus before it exploded in 1918. What emerges is a surprising tale with many players and plot lines, in which echoes of prior pandemics, imprinted in the immune responses of those alive in 1918, set the stage for the catastrophe. I will also discuss how resolving the mysteries of 1918 could help to prevent future pandemics and to control seasonal influenza, which quietly kills millions more every decade.