Youth with substance use disorder frequently have co-occurring psychiatric symptoms/diagnoses. Moreover, children and adolescents with mental health symptoms are highly vulnerable to initiating substance use, including nonmedical use of prescription opioids. This webinar is aimed at general pediatricians and pediatric subspecialists but all clinicians who work with youth will find this useful. First, a review of relevant clinical epidemiology on co-occurring psychiatric illness and substance use disorder is provided followed by an overview of clinical tools to aid in recognizing symptoms of common psychiatric illness. Trends in adolescent substance use change quickly but primary care providers are most likely to encounter issues related to tobacco, alcohol and cannabis. A demonstration of sample approaches to substance use screening with a focus on detecting risk in settings where opioids may be prescribed is also offered. This clinical issue is a complex one as differentiating which came first (substance use disorder or mental health condition) is not always obvious, especially in the face of contemporary psychosocial issues in adolescents.