There have been dramatic changes worldwide in the attitudes toward and consumption of recreational and medical cannabis. Cannabinoid receptors, which mediate the actions of cannabis, are abundantly expressed in brain regions known to mediate neural processes underlying reward, cognition, emotional regulation and stress responsivity relevant to addiction vulnerability. Despite debates regarding potential pathological consequences of cannabis use, cannabis use disorder is a clinical diagnosis with high prevalence in the general population and that often has its genesis in adolescence and in vulnerable individuals associated with psychiatric comorbidity, genetic and environmental factors. Integrated information from human and animal studies is beginning to expand insights regarding neurobiological systems associated with cannabis use disorder, which often share common neural characteristics with other substance use disorders, that could inform prevention and treatment strategies.