This paper analyzes the influence of illicit drug use on highway fatal outcomes by estimating regression models using data for the 48 contiguous U.S. states for the years 2009 and 2010. The models include a representative, but not exhaustive, collection of roadway fatality determinants. The impact of illicit drug usage on the motor vehicle death rate differs across age groups. There are statistically significant life-taking effects from marijuana use by the very youngest drivers. Comparable effects from the usage of cocaine and nonmedical pain relievers occur among older drivers. Negatively associated with the highway death rate and statistically significant are real per capita income and seat belt use. Statistically significant positive relationships with the rate are found for the ratio of rural to urban driving, temperature, speed limit, the percentage of older drivers, and cell phone usage. The paper provides information to policy makers at a time when state-level drug laws are changing rapidly. Evidence reported here on how drug use affects highway fatal outcomes is relevant to that discussion.