The emergence of the 2009 H1N1 influenza epidemic produced a number of unique communication challenges for the Centers for Disease Control and Prevention (CDC). Part of the CDC’s response to these challenges included the strategic use of video posted to YouTube to address the public’s need for information in a timely and accessible way. This case study includes an examination of the context in which this communication response took place, an overview of the research and strategy development that informed the strategic communication, and an evaluation of the response.