To systematically review evidence evaluating cannabis-related knowledge and perception of risk in children and adolescents. We systematically searched Medline, PsycINFO, and EMBASE using Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. 133 studies from around the world (including ages 10-18 yrs) met inclusion criteria, with 70% meeting grade 2C quality. Increased knowledge and perception of risk of cannabis frequently correlated with lower levels of current use and intent to use. Studies examining correlations over time generally demonstrated increased adolescent cannabis use and decreased perception of risk. Included prevention-based interventions often enhanced knowledge and/or perception of risk in adolescents exposed to the intervention. Studies exploring outcomes relating to legislative changes for recreational marijuana use demonstrated considerable heterogeneity regarding knowledge and perception of risk whereas studies that focused on medicinal marijuana legislative changes overwhelmingly demonstrated a decrease in perception of risk post legalization. Increased knowledge and perception of risk of cannabis in adolescents often correlate with lower levels of current use and intention to use in the future. Further study and implementation of public health and clinically-oriented strategies that seek to increase knowledge among youth about the potential health harms of cannabis use should continue and be prioritized. [Author's abstract]