This guide offers strategies from the best available evidence to assist in planning to prevent or delay substance use initiation, decrease substance use, and encourage substance use cessation. It includes six strategies to prevent youth substance use, each with several approaches, and evidence to support each approach. The strategies can be tailored to address various communities’ needs. A strategy is a broad action that can help prevent youth substance use, while an approach is a specific way to implement that strategy. Specific intervention or program names will only be used in the evidence sections to support the strategy and approach. Each strategy includes a set of associated outcomes from the studies reviewed in that strategy. The outcomes include substance use risk and protective factors, along with substance use behaviors. This is not an exhaustive list, and not every intervention, program, or policy included in that section addresses each of the included outcomes. A list of strategies and programs mentioned can be found in Appendix I.