The 1918 flu pandemic (the "Spanish flu") was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus (the second was the 2009 flu pandemic, an outbreak of swine flu). It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin. Most victims were healthy young adults, in contrast to most influenza outbreaks, which predominantly affect juvenile, elderly, or weakened patients. The flu pandemic was implicated in the outbreak of encephalitis lethargica in the 1920s.

The pandemic lasted from January 1918 to December 1920, spreading even to the Arctic and remote Pacific islands. Between 50 and 130 million died, making it one of the deadliest natural disasters in human history. Even using the lower estimate of 50 million people, 3% of the world's population (which was 1.86 billion at the time) died of the disease. Some 500 million, or 27%, were infected.

Tissue samples from frozen victims were used to reproduce the virus for study. This research concluded, among other things, that the virus kills through a cytokine storm (overreaction of the body's immune system), which perhaps explains its unusually severe nature and the concentrated age profile of its victims. The strong immune system reactions of young adults ravaged the body, whereas the weaker immune systems of children and middle-aged adults resulted in fewer deaths.

An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in recent history. Pandemics can cause high levels of mortality, with the Spanish influenza estimated as being responsible for the deaths of over 50 million people. There have been about three influenza pandemics in each century for the last 300 years. The most recent one was the 2009 flu pandemic.

Influenza pandemics occur when a new strain of the influenza virus is transmitted to humans from another animal species. Species that are thought to be important in the emergence of new human strains are pigs, chickens and ducks. These novel strains are unaffected by any immunity people may have to older strains of human influenza and can therefore spread extremely rapidly and infect very large numbers of people. Influenza A viruses can occasionally be transmitted from wild birds to other species causing outbreaks in domestic poultry and may give rise to human influenza pandemics. The transportation of influenza viruses throughout the world is thought in part to be by bird migrations, though commercial shipments of live bird products might also be implicated, as well as human travel plans.