Abstract Purpose of Review To review the literature on the trends in substance use among youth during the coronavirus SARS-CoV-2 (COVID-19) pandemic. Recent Findings The pandemic has given rise to concerns about the mental health and social well-being of youth, including its potential to increase or exacerbate substance use behaviors. This systematic review identified and included 49 studies of use across alcohol, cannabis, tobacco, e-cigarettes/vaping, and other drugs, and unspecified substances. The majority of studies across all categories of youth substance use reported reductions in prevalence, except in the case of other drugs and unspecified drug and substance use, which included three studies that reported an increase in use and three studies that reported decrease in use. Summary Overall, the results of this review suggest that the prevalence of youth substance use has largely declined during the pandemic. Youth substance use in the post-pandemic years will require monitoring and continued surveillance.