The use of alcohol, tobacco and illicit drugs entails considerable burden of disease: in 2000, about 4% of the global burden as measured in disability adjusted life years was attributable to each alcohol and tobacco, and 0.8% to illicit drugs. The burden of alcohol in the above statistic was calculated as net burden, i.e. incorporating the protective health effects. Tobacco use was found to be the most important of 25 risk factors for developed countries in the comparative risk assessment underlying the data. It had the highest mortality risk of all the substance use categories, especially for the elderly. Alcohol use was also important in developed countries, but constituted the most important of all risk factors in emerging economies. Alcohol use affected younger people than tobacco, both in terms of disability and mortality. The burden of disease attributable to the use of legal substances clearly outweighed the use of illegal drugs. A large part of the substance-attributable burden would be avoidable if known effective interventions were implemented.