In the United States, as much as 20 percent of the land surface is considered karst, and 40 percent of the groundwater for municipal and domestic consumption comes from karst aquifers. The U.S. Environmental Protection Agency has recognized karst aquifers as the groundwater type most vulnerable to contamination from anthropogenic sources, including hazardous materials and other pollutants. This paper presents a series of recommendations to assist first responders, water resource managers, and community leaders during a hazardous materials release in karst terrains. Hazardous materials releases have the potential to adversely impact human health and the environment. Karst aquifers are noted for rapid and direct recharge through caves, sinkholes, and sinking streams; groundwater velocities can exceed 1 km per day and are often complex and poorly understood. Best management practices in karst include pre-event planning, response, remediation, and long-term monitoring for hazardous materials releases.