The purpose of this Funding Opportunity Announcement (FOA) is to encourage pilot and/or feasibility research in the following areas: 1) the development and pilot testing of new or adapted interventions to prevent or delay the initiation of substance use and/or the progression from use to misuse or disorder and 2) pre-trial feasibility and acceptability testing of services and service system research relevant to the prevention of substance use. In addition to the prevention of substance use, misuse and disorder, other outcomes of interest for the research supported through FOA include a reduction in negative sequalae such as deaths related to impaired driving, suicidal behavior (e.g., nonfatal and fatal attempts), and drug- or alcohol-related acquisition or transmission of HIV infection and viral hepatitis among diverse populations and settings.