Until recently, most information about substance use in the United States has come from large urban areas. Today, we recognize that substance use and misuse affects every region in the United States. The mission of the Rural Drug Addiction Research (RDAR) Center is to apply complementary approaches across a variety of disciplines to better understand the causes and consequences of substance use and identify new avenues to address substance use problems. Our Center brings together basic and health scientists from neuroscience, cognition, simulation, epidemiology, psychology, and sociology to address the etiology, assessment, prevention, and treatment of this critical public health challenge. Our vision is to understand substance use and misuse from synapse to society. Center projects are supported by RDAR’s Administrative Core and the Longitudinal Networks Core (RDAR’s Research Core) to expand our impact and contributions from work on substance use and related health disparities.