Public health officials investigate outbreaks to control them, to prevent additional illnesses, and to learn how to prevent similar outbreaks in the future. The process the public health community uses to detect, investigate, and control enteric (intestinal) disease outbreaks from food, water, and other sources involves certain procedural steps. These include detecting a possible outbreak, defining and finding cases, generating hypotheses about likely sources, testing the hypotheses and evaluating evidence, finding contamination sources, controlling the outbreak, and determining when the outbreak is over. Investigating outbreaks of acute enteric diseases can be a dynamic and complex undertaking involving multiple public health and regulatory partners in different jurisdictions. This chapter provides an overview of the investigation process with an emphasis on multijurisdictional foodborne illness investigations in the United States.