This study examined if (1) there is an association in the general population between cannabis use, DSM-IV abuse and dependence, and other substance use and DSM-IV substance abuse/dependence; (2) if so, is it explained by demographic characteristics or levels of neuroticism? It used data from the Australian National Survey of Mental Health and Well-Being (NSMHWB), a stratified, multistage probability sample of 10,641 adults, representative of the general population. DSM-IV diagnoses of substance abuse and dependence were derived using the Composite International Diagnostic Interview (CIDI). There was a strong bivariate association between involvement with cannabis use in the past 12 months and other substance use, abuse and dependence. In particular, cannabis abuse and dependence were highly associated with increased risks of other substance dependence. These associations remained after including other variables in multiple regression. Cannabis use without disorder was strongly related to other drug use, an association that was not explained by other variables considered here. The high likelihood of other substance use and substance use disorders needs to be considered among persons seeking treatment for cannabis use problems.