People use a drug at a particular point in time because they like what it does to their brain. Drugs modify mood, perception, and psychological state. This occurs through the mediational process of altering the brain. Prolonged drug use changes the brain in fundamental and long-lasting ways. These long-lasting brain changes are a major component of the addiction itself. It is as though there were a switch in the brain that flips at some point during an individual's drug use. The switch flips at different points for different individuals, changing the person from a drug user/abuser to a drug addict. Although the precise molecular nature of this switch is not yet known, there is some understanding of the mechanisms involved when brain changes occur. Current knowledge implicates activation of the brain's mesolimbic dopamine system as a common denominator in at least the acute effects of all drugs of abuse. Addiction, however, is more than just a brain disease; it occurs in an important set of contexts -- environmental, historical, and physiological -- that affect the way in which drug use interacts with the brain. The most effective drug treatments simultaneously attend to the biological, the behavioral, and the social contexts. Both health practitioners and the general public must accept that drug addiction is a biomedical problem rather than a social problem or a failure of will; only in the context of such knowledge will appropriate drug-control policy and treatment be developed. 2 figures