This issue of the Journal is focused on providing a deeper understanding of the factors underlying alcohol and cannabis use and misuse in relation to the development of substance use disorders and interactions with other psychiatric illnesses. The prevalence of alcohol use disorder in the United States is high. Data from 2019 suggest that 14.5 million individuals age 12 or older suffered with alcohol use disorder (1). It is important to note that alcohol misuse substantially contributes to premature death, which is largely due to alcohol-related accidents, suicides, and medical illnesses. According to the World Health Organization, 5.3% of all deaths worldwide in 2016 were related to alcohol use (2). Cannabis use in the United States is also very common and, notwithstanding federal regulations, numerous states have legalized its recreational and medical use. In 2018, it was estimated that 11.8 million adolescents and young adults used cannabis in the past year (3). Frequent, chronic, and heavy cannabis use can lead to cannabis use disorder, which can be associated with psychosocial dysfunction, effects on cognition and memory, reduced motivation, and alterations in mood and anxiety regulation.The centerpiece of this issue is an overview on cannabis use, authored by Dr. Margaret Haney from Columbia University, that reviews cannabinoid substances and the endogenous cannabinoid system in relation to cannabinoid abuse and its treatment (4). This overview sets the stage for the accompanying original research papers that examine cannabis use in U.S. veterans, the relation between cannabis use and psychotic disorders, and interactions between cannabis and alcohol use and eating disorders. In addition to the editorials commenting on these papers, we include a piece in which the Journal's Editors highlight papers published in 2021 that they found to be particularly impactful (5).