Climate change is undermining the mental and physical health of global populations, but the question of how it is affecting substance-use behaviors has not been systematically examined. In this narrative synthesis, we find that climate change could increase harmful substance use worldwide through at least five pathways: psychosocial stress arising from the destabilization of social, environmental, economic, and geopolitical support systems; increased rates of mental disorders; increased physical-health burden; incremental harmful changes to established behavior patterns; and worry about the dangers of unchecked climate change. These pathways could operate independently, additively, interactively, and cumulatively to increase substance-use vulnerability. Young people face disproportionate risks because of their high vulnerability to mental-health problems and substance-use disorders and greater number of life years ahead in which to be exposed to current and worsening climate change. We suggest that systems thinking and developmental life-course approaches provide practical frameworks for conceptualizing this relationship. Further conceptual, methodological, and empirical work is urgently needed to evaluate the nature and scope of this burden so that effective adaptive and preventive action can be taken.