The 1918 "Spanish" influenza pandemic, which caused approximately 50 million deaths worldwide, remains a significant public health concern. The origins, epidemiological features, and pathogenicity of the 1918 virus are still not fully understood. New genetic sequencing data have provided insights into the virus's genome, but critical questions about its origin and mechanisms of pathogenicity remain unanswered. The 1918 virus is believed to have originated from an avian-like influenza virus, possibly derived from an unknown source, and it likely spread simultaneously in three distinct waves across Europe, Asia, and North America in 1918-1919. The virus's unique characteristics, such as its high case-fatality rate among young adults and the rapidity of its three waves, have led to speculation about its genetic and host factors. Despite ongoing research, the exact reasons for the 1918 pandemic's severity and its ability to cause successive waves remain enigmatic. Understanding the 1918 pandemic is crucial for preparing against future pandemics, especially those caused by viruses like H5N1.The 1918 "Spanish" influenza pandemic, which caused approximately 50 million deaths worldwide, remains a significant public health concern. The origins, epidemiological features, and pathogenicity of the 1918 virus are still not fully understood. New genetic sequencing data have provided insights into the virus's genome, but critical questions about its origin and mechanisms of pathogenicity remain unanswered. The 1918 virus is believed to have originated from an avian-like influenza virus, possibly derived from an unknown source, and it likely spread simultaneously in three distinct waves across Europe, Asia, and North America in 1918-1919. The virus's unique characteristics, such as its high case-fatality rate among young adults and the rapidity of its three waves, have led to speculation about its genetic and host factors. Despite ongoing research, the exact reasons for the 1918 pandemic's severity and its ability to cause successive waves remain enigmatic. Understanding the 1918 pandemic is crucial for preparing against future pandemics, especially those caused by viruses like H5N1.