Cannabis and cannabinoids are widely used, both as recreational substances with potential for addiction, and as treatments for a number of disorders. A large body of literature has investigated the harmful and/or beneficial effects of cannabis and/or cannabinoids employing observational and interventional methodologies. These individual studies have been pooled in many meta-analyses. Further, Mendelian Randomization (MR) studies have reported on a causal association between cannabis use and certain outcomes. This chapter reviews existing meta-analyses that pooled observational and interventional studies, and MR studies reporting on health outcomes after exposure to cannabis and/or cannabinoids in the general population, and selected clinical populations. We show that evidence from observational, interventional, and MR studies point towards an association between cannabis and psychosis. Several additional detrimental effects of cannabis emerged, including other psychiatric symptoms, cognitive impairment, and risk of motor vehicle accident (MVA). In terms of therapeutic benefits, cannabidiol seems to be effective for certain types of epilepsy, notably in children. Also, cannabis-based medicines can be effective in improving muscle spasticity in multiple sclerosis, ameliorating chronic pain syndromes, and reducing nausea/vomiting in palliative care settings. Risk–benefit ratios should be discussed with individual patients.