The overdose crisis among U.S. adolescents has become a significant public health concern, with an average of 22 adolescents dying from drug overdoses each week in 2022. Drug overdoses and poisonings are now the third-leading cause of pediatric deaths in the United States, surpassing firearm-related injuries and motor vehicle crashes. Despite a decline in reported drug use among adolescents, the crisis has intensified, with fentanyl involvement in at least 75% of adolescent overdose deaths. The widespread availability of counterfeit pills containing fentanyl is a major driver of this increase. To address the crisis, clinicians, parents, educators, and policymakers must take immediate action. Three groups at high risk are identified: adolescents experimenting with substances, those with mental illness or trauma, and those with opioid use disorder (OUD). Many adolescents who overdose do not have a known OUD, highlighting the need for widespread overdose prevention education. Pediatricians and mental health practitioners should routinely screen adolescents for substance use and provide guidance on fentanyl, counterfeit pills, and overdose reversal agents like naloxone. Educators and parents should convey clear messages about the risks of fentanyl and counterfeit pills, expanding prevention programming to include education on these substances. Social media platforms can be leveraged to disseminate accurate information and reduce stigma. Additionally, long-term strategies require accessible and high-quality mental health care and addiction treatment, particularly for underserved communities. Addressing disparities in overdose deaths based on race and ethnicity and targeting geographic hotspots are also crucial. Overall, the U.S. overdose crisis demands a comprehensive approach involving multiple stakeholders to ensure adolescents have the knowledge and resources to stay safe and access necessary support.The overdose crisis among U.S. adolescents has become a significant public health concern, with an average of 22 adolescents dying from drug overdoses each week in 2022. Drug overdoses and poisonings are now the third-leading cause of pediatric deaths in the United States, surpassing firearm-related injuries and motor vehicle crashes. Despite a decline in reported drug use among adolescents, the crisis has intensified, with fentanyl involvement in at least 75% of adolescent overdose deaths. The widespread availability of counterfeit pills containing fentanyl is a major driver of this increase. To address the crisis, clinicians, parents, educators, and policymakers must take immediate action. Three groups at high risk are identified: adolescents experimenting with substances, those with mental illness or trauma, and those with opioid use disorder (OUD). Many adolescents who overdose do not have a known OUD, highlighting the need for widespread overdose prevention education. Pediatricians and mental health practitioners should routinely screen adolescents for substance use and provide guidance on fentanyl, counterfeit pills, and overdose reversal agents like naloxone. Educators and parents should convey clear messages about the risks of fentanyl and counterfeit pills, expanding prevention programming to include education on these substances. Social media platforms can be leveraged to disseminate accurate information and reduce stigma. Additionally, long-term strategies require accessible and high-quality mental health care and addiction treatment, particularly for underserved communities. Addressing disparities in overdose deaths based on race and ethnicity and targeting geographic hotspots are also crucial. Overall, the U.S. overdose crisis demands a comprehensive approach involving multiple stakeholders to ensure adolescents have the knowledge and resources to stay safe and access necessary support.