Editors' Summary: Regulation of hazardous materials (HAZMAT) transportation has developed in a piecemeal fashion over the past century. In response, Congress passed the Hazardous Materials Transportation Act in 1975 and the Hazardous Materials Transportation Uniform Safety Act in 1990, delegating authority to the U.S. Department of Transportation (DOT) to improve effectiveness, consistency, and uniformity in HAZMAT regulation. The U.S. EPA also participates in HAZMAT regulation under the Resource Conservation and Recovery Act. This Article traces the history of HAZMAT regulations, identifies the regulators and the regulated communities, and delineates the DOT's enforcement responsibilities in cooperation with other federal agencies. The Article also assesses the strengths and weaknesses of the HAZMAT regulations by focusing on the U.S. role in world chemical markets and on states' rights issues under the Tenth Amendment of the U.S. Constitution. Finally, the authors conclude that the HAZMAT requirements tell industry what is expected and allow for innovative means of compliance.