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This paper summarises data for the prevalence, correlates, and probable adverse health consequences of problem use of amphetamines, cannabis, cocaine, and opioids. We discuss findings from systematic reviews of the prevalence of illicit drug use and dependence, remission from dependence, and mortality in illicit drug users, and evidence for acute and chronic effects of illicit drug use. We outline the regional and global distribution of use and estimated health burden from illicit drugs. These distributions are likely to be underestimates because they have not included all adverse outcomes of drug use and exclude those of cannabis–the mostly widely used illicit drug. In high-income countries, illicit drug use contributes less to the burden of disease than does tobacco but a substantial proportion of that due to alcohol. The major adverse health effects of cannabis use are dependence and probably psychotic disorders and other mental disorders. The health-related harms of cannabis use differ from those of amphetamine, cocaine, and opioid use, in that cannabis contributes little to mortality. Intelligent policy responses to drug problems need better data for the prevalence of different types of illicit drug use and the harms that their use causes globally. This need is especially urgent in high-income countries with substantial rates of illicit drug use and in low-income and middle-income countries close to illicit drug production areas.