In the event of a terrorist attack or catastrophic release involving potential chemical and/or biological warfare agents, decisionmakers will need to make timely and informed choices about whether, or how, to respond. The objective of this article is to provide a decision framework to specify initial and follow-up actions, including possible decontamination, and to address long-term health and environmental issues. This decision framework consists of four phases, beginning with the identification of an incident and ending with verification that cleanup and remediation criteria have been met. The flowchart takes into account both differences and similarities among potential agents or toxins at key points in the decision-making process. Risk evaluation and communication of information to the public must be done throughout the process to ensure a successful effort.