The National Institute on Drug Abuse (NIDA) is the lead federal agency supporting scientific research on drug use and addiction. After decades of research, we now understand substance use disorders (SUDs) to be chronic but treatable brain disorders that emerge from the complex interplay of biological, social, and developmental factors. Adverse social determinants of health enable biological vulnerabilities to SUDs to emerge, just as protective factors in one’s social environment reduce the risk of substance use and addiction. NIDA-supported research has illuminated these risk and protective factors and led to the development of effective prevention and treatment interventions, providing hope for the more than 40 million people in the United States with SUDs and their loved ones. Yet, NIDA’s mission remains critical, given the challenges that SUDs present to the nation today.