Objectives: To conduct a comprehensive search of the peer-reviewed literature to assess risk of cannabis-related mortality. Methods: Systematic peer reviewed literature searches were conducted in Medline, EMBASE and PsycINFO to identify data on mortality associated with cannabis use. Search strings for cannabis and mortality, tailored to each database (including keywords, MeSH terms, EMTREE terms and explode terms) were used. Searches were limited to human subjects and the publication timeframe of January 1990 to January 2008. The reference lists of review articles and of specific studies deemed important by colleagues, were searched to identify additional studies that may not have been identified in the electronic database search. A list of the selected articles was emailed to experts in the field asking for comment on completeness. Results: At present there is insufficient evidence to suggest that the all-cause mortality rate is elevated among cannabis users in the general population but regular cannabis use may increase risk in vulnerable populations such as those with cardiovascular disease. Case- control studies suggest that some outcomes may be elevated among heavy cannabis users, namely, fatal motor vehicle accidents, and possibly respiratory and brain cancers. The evidence is as yet unclear as to whether regular cannabis use increases the risk of suicide. Finally, lifetime cannabis has not been associated with mortality or other outcomes. Conclusions: There is a need for long-term cohort studies that follow cannabis using individuals into old age, when the likelihood of any detrimental effects of cannabis use are more likely to emerge among those who persist in using cannabis into middle age and older.