Dating back to antiquity, influenza pandemics have posed the greatest threat of a worldwide calamity caused by infectious disease. Over the past 300 years, 10 influenza pandemics have occurred among humans. The most recent came in 1957-58 and 1968-69, and although several tens of thousands of Americans died in each one, these were considered mild compared to others. The 1918-19 pandemic was not. According to recent analysis, it killed 50 to 100 million people globally. Today, with a population of 6.5 billion, more than three times that of 1918, even a “mild” pandemic could kill many millions of people. A number of recent events and factors have significantly heightened concern that a specific near-term pandemic may be imminent. It could be caused by H5N1, the avian influenza strain currently circulating in Asia. At this juncture scientists cannot be certain. Nor can they know exactly when a pandemic will hit, or whether it will rival the experience of 1918-19 or be more muted like 1957-58 and 1968-69. The reality of a coming pandemic, however, cannot be avoided. Only its impact can be lessened. Some important preparatory efforts are under way, but much more needs to be done by institutions at many levels of society.