The U.S. adolescent overdose crisis has escalated sharply, with over 22 adolescents dying each week from drug overdoses in 2022, making it the third leading cause of pediatric deaths. Despite a decline in illicit drug use among adolescents, overdose deaths have more than doubled since 2019, driven largely by the availability of counterfeit pills containing fentanyl, which is now involved in at least 75% of adolescent overdose deaths. Fentanyl, initially used as a substitute for heroin, is now increasingly found in counterfeit pills resembling prescription drugs, which are more likely to be used by adolescents for experimentation. The crisis requires urgent action from clinicians, parents, educators, and policymakers. Three groups of adolescents at risk include those experimenting with substances without opioid use disorder (OUD), those with mental illness or trauma, and those with OUD. Many overdose victims do not have a known OUD. Education on fentanyl, counterfeit pills, and naloxone is essential, as most overdose deaths are unintentional. Clinicians should screen adolescents for substance use and provide guidance on recognizing and responding to overdoses. Educators and parents should emphasize the risks of fentanyl and counterfeit pills, while avoiding fear-based messaging. The Safety First curriculum promotes abstinence but also provides risk-reduction strategies. Schools should implement naloxone access, no-questions-asked pill-disposal programs, and anonymous resources for students. Social media, though a risk factor, can also be used for education. Public health efforts must address racial and geographic disparities, with a focus on Native-led initiatives and hotspots like Arizona, Colorado, and Washington. Long-term solutions require accessible, affordable mental health and addiction treatment, as well as reducing stigma. The elimination of the X-waiver requirement for buprenorphine has expanded treatment options. Parents, physicians, and educators must equip adolescents with knowledge and tools to stay safe, while supporting mental health and addiction services.The U.S. adolescent overdose crisis has escalated sharply, with over 22 adolescents dying each week from drug overdoses in 2022, making it the third leading cause of pediatric deaths. Despite a decline in illicit drug use among adolescents, overdose deaths have more than doubled since 2019, driven largely by the availability of counterfeit pills containing fentanyl, which is now involved in at least 75% of adolescent overdose deaths. Fentanyl, initially used as a substitute for heroin, is now increasingly found in counterfeit pills resembling prescription drugs, which are more likely to be used by adolescents for experimentation. The crisis requires urgent action from clinicians, parents, educators, and policymakers. Three groups of adolescents at risk include those experimenting with substances without opioid use disorder (OUD), those with mental illness or trauma, and those with OUD. Many overdose victims do not have a known OUD. Education on fentanyl, counterfeit pills, and naloxone is essential, as most overdose deaths are unintentional. Clinicians should screen adolescents for substance use and provide guidance on recognizing and responding to overdoses. Educators and parents should emphasize the risks of fentanyl and counterfeit pills, while avoiding fear-based messaging. The Safety First curriculum promotes abstinence but also provides risk-reduction strategies. Schools should implement naloxone access, no-questions-asked pill-disposal programs, and anonymous resources for students. Social media, though a risk factor, can also be used for education. Public health efforts must address racial and geographic disparities, with a focus on Native-led initiatives and hotspots like Arizona, Colorado, and Washington. Long-term solutions require accessible, affordable mental health and addiction treatment, as well as reducing stigma. The elimination of the X-waiver requirement for buprenorphine has expanded treatment options. Parents, physicians, and educators must equip adolescents with knowledge and tools to stay safe, while supporting mental health and addiction services.