In April 2009, the Centers for Disease Control and Prevention confirmed 2 cases of 2009 pandemic influenza A (H1N1) virus infection in children from southern California, marking the beginning of what would be the first influenza pandemic of the twenty-first century. This report describes the epidemiology of the 2009 H1N1 pandemic in the United States, including characterization of cases, fluctuations of disease burden over the course of a year, the age distribution of illness and severe outcomes, and estimation of the overall burden of disease.