Alcohol and cannabis are the most commonly used substances during adolescence and are typically initiated during this sensitive neurodevelopmental period. The aim of this review is to provide a comprehensive overview of the most recent literature focused on understanding how these substances affect the developing brain.Articles included in this review were identified by entering 30 search terms focused on substance use, adolescence, and neurodevelopment into MEDLINE, Embase, PsycINFO, ProQuest Central, and Web of Science. Studies were eligible for inclusion if they longitudinally examined the effect of adolescent alcohol and/or cannabis use on structural or functional outcomes in 50 or more participants.More than 700 articles were captured by the search, and 43 longitudinal studies met inclusion criteria, including 18 studies focused on alcohol use, 13 on cannabis use, and 12 on alcohol and cannabis co-use.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.