The 1918 influenza pandemic was the most lethal single event in modern history. Besides its mortality the 1918 pandemic was unusual for several reasons. It preferentially killed young adults from 20 to 40 y with a peak mortality at age 28 y. Mortality was highly variable with death rates varying by at least 10 fold within similar groups of citizens, soldiers, cities and islands. Secondary bacterial pneumonia following influenza was the overwhelming cause of death and not viral pneumonitis or acute lung injury. Clinical expressions of the 1918 pandemic were unusual with bleeding into the respiratory tree including epistaxis and dark blue cyanotic skin. The 1918 influenza virus apparently ceased circulation in the human population in the early 1920s but continued to evolve in pigs. Immunizations using viruses from 1918 and 2009 can cross-protect laboratory animals even though the human mortality outcomes were very different between the first pandemics of the 20th and 21st centuries. Unusual aspects of historical epidemics may help to reconstruct what actually occurred in 1918 and thus better prepare for the next pandemic.