Successful detonation of an improvised nuclear device (IND) would be a catastrophic event, causing an unprecedented number of injuries and lives lost, as well as economic, political, and social disruption. However, an effective medical response and an infrastructure prepared to protect itself from fallout could save tens of thousands of lives. Since 2001, all levels of government, academic institutions, and professional organizations have done significant work to enhance our ability to prepare for and respond to a nuclear detonation. The following manual is intended to simplify and translate the necessary protective actions and medical response modalities in order to make them more accessible and easier to translate into practice. The approach of this manual is to provide a common baseline application for various allied response disciplines (to include senior operational responders, emergency managers, public health advisors, and municipal, State, and Federal executives and elected officials). This manual will enhance mutual understanding of the basics of nuclear response.