Although the pandemic’s impact on youth mental health is garnering significant attention, youth substance use problems are often overlooked or treated as a disciplinary issue within schools. This brief examines school-based approaches to address youth substance use in the District of Columbia, Massachusetts, and New Mexico. We find that schools can become an effective place for substance use interventions by

• explicitly integrating substance use services in behavioral health initiatives,
• cultivating a positive school environment,
• reframing youth substance use as a health condition, and
• partnering with culturally effective adolescent substance use care providers and youth-serving organizations in the community.

Medicaid programs could better support school-based substance use services by creating youth-specific prevention and early intervention benefits and developing payment models that account for nonclinical activities school-based providers may undertake when working with adolescents. The education and health care systems, policymakers, philanthropy, parents, and community members can also support schools in becoming more nurturing spaces that promote the overall health and wellness of youth and have the knowledge and resources to respond with evidence-informed and equity-focused health approaches before substance use turns into a chronic, life-altering disorder.