The range of harms to health from psychoactive substances is considered, and current data are presented on the health burden of alcohol, tobacco, and illicit drugs. Four major strategies for preventing or reducing harm are discussed: education and persuasion, treatment, insulating use from harm, and regulating the availability and conditions of use. Education and treatment are necessary parts of an overall public health approach, but are not very effective in themselves in reducing rates of harm in the population. Insulating use from harm and regulating availability have often proved effective components of a public health approach.