The 1918-1919 H1N1 influenza pandemic was among the most deadly events in recorded human history, killing an estimated 50-100 million persons. Because recent H5N1 avian epizootics have been associated with sporadic human fatalities, concern has been raised that a new pandemic, as fatal as the pandemic of 1918, or more so, could be developing. Understanding the events and experiences of 1918 is thus of great importance. However, despite the genetic sequencing of the entire genome of the 1918 virus, many questions about the 1918 pandemic remain. In this review we address several of these questions, concerning pandemic-virus origin, unusual epidemiologic features, and the causes and demographic patterns of fatality. That none of these questions can yet be fully answered points to the need for continued pandemic vigilance, basic and applied research, and pandemic preparedness planning that emphasizes prevention, containment, and treatment with antiviral medications and hospital-based intensive care.