Rural youth and young adults have historically had higher use rates of alcohol and other substances than their urban counterparts. Recent research suggests that rates of youth and young adult alcohol and other substance use have declined during the last two decades, but limited knowledge exists on whether and how current rural and urban substance use patterns may differ. As national substance use rates decline, it is important to reassess differences in use among rural versus urban youth and young adults. This study uses data from the National Survey of Drug Use and Health (NSDUH) to examine rural-urban differences in the rates of substance use among youth and young adults. Findings can help inform rural-specific prevention strategies and research targeting rural communities.