We examined the role of stress as a risk factor and motivation for cannabis use/misuse. A systematic review of studies gathered from PsychINFO and MEDLINE databases was conducted. Findings suggest that cannabis is commonly used as a stress-coping strategy. Negative life events, trauma, and maladaptive coping were all related to consumption. Cannabis use for stress-coping purposes was most evident when examining chronic as compared with experimental use. Although many individuals may be able to use cannabis without consequences, there appears to be a subset of individuals who experience greater life stress and who may be more likely to use for stress-coping purposes. These individuals may be at greatest risk for addiction. Chronic use may potentiate stress-related motivation to use/abuse cannabis and is associated with decision-making deficits and alterations in brain-stress pathways that may exacerbate compulsive drug seeking and sensitize individuals to stress-related drug use. Overall, stress-coping interventions and harm reduction focused on reducing the amount ingested may facilitate prevention and recovery efforts.