The legality, recreational and medical use of cannabis varies widely by country and region but remains largely prohibited internationally. In October 2018, Canada legalized the recreational use of cannabis—a move many viewed as controversial. Proponents of legalization have emphasized the potential to eradicate the marijuana black market, improve quality and safety control, increase tax revenues, improve the availability of medical cannabis, and lower gang-related drug violence. Conversely, opponents of legalization have stressed concerns about cannabis’ addictive potential, second-hand cannabis exposure, potential exacerbation of underlying and established mental illnesses, as well as alterations in perception that affect safety, particularly driving. This systematic review synthesizes recent international literature on the clinical and public health implications of cannabis legalization.