Existing studies suggest heavy alcohol and cannabis use during adolescence are related to small to moderate disruptions in brain structure and function, as well as neurocognitive impairment. The effects of alcohol use include widespread decreases in gray matter volume and cortical thickness across time; slowed white matter growth and poorer integrity; disrupted network efficiency; and poorer impulse and attentional control, learning, memory, visuospatial processing, and psychomotor speed. The severity of some effects is dependent on dose. Heavy to very heavy cannabis use is associated with decreased subcortical volume and increased frontoparietal cortical thickness, disrupted functional development, and decreased executive functioning and IQ compared to non-using controls. Overall, co-use findings suggest more pronounced effects related to alcohol use than to cannabis use. Several limitations exist in the literature. Sample sizes are relatively small and demographically homogenous, with significant heterogeneity in substance use patterns and methodologies across studies. More research is needed to clarify how substance dosing and interactions between substances, as well as sociodemographic and environmental factors, affect outcomes. Larger longitudinal studies, already underway, will help clarify the relationship between brain development and substance use.