Over the entire period from 1990 to 2017, increasing trends were identified in the proportions of study pilots testing positive for at least one drug categorized as potentially impairing, used to treat a potentially impairing condition, or as a controlled substance. • Pilot education regarding appropriate and inappropriate medication choices is increasingly important because of the rising trend of positive test results for potentially impairing drugs. • The Federal Aviation Administration’s November 2019 fact sheet on pilots and medication and over-the-counter medication guidance document provide easy-to-understand information to educate pilots about potentially impairing drugs and make them aware of less impairing alternative drugs. • Increasing evidence of marijuana use by pilots in this research update indicates a safety hazard that has not been effectively addressed. • The continuing increase in the prevalence of potentially impairing drug use by fatally injured pilots further supports the need for research to better understand the relationship between drug use and accident risk.