Like their peers in the general youth population, YCMC are at risk of experimentation and regular substance use, including non-medical use of prescription medications. However, given dangerous disease-substance interactions, the stakes for detecting and intervening on substance use are perhaps even higher for YCMC. Given risk for non-adherence with chronic disease management among substance-using youth, it is incumbent on primary care providers, specialty providers, and behavioral health specialists to be vigilant in asking about substance and providing brief counseling and referral to formal substance use treatment when appropriate. Doing so is not only likely to prevent the direct harm of alcohol and drug use, but also to simultaneously improve chronic disease treatment outcomes.