Background: Cannabis is the most widely used illicit drug in Australia. Regular use has been associated with increased risk for a range of harms, including the development and exacerbation of mental disorders. Objective: This article reviews current evidence relating to the neuropharmacology of cannabis and its impact on mental health, as well as strategies related to the assessment and management of cannabis and co-occurring mental disorders within the primary care setting. Discussion: Early and heavy use of cannabis has been associated with the onset of psychosis and depression, while chronic use results in poorer treatment outcomes among those with co-occurring mental disorders. Effective management involves the development of therapeutic engagement and an ongoing relationship, with monitoring of cannabis use and mental health problems. Standard pharmacotherapeutic treatment of the mental disorder may be associated with a reduction in cannabis use, although adjunctive psychological intervention is also likely to be required.