Repetitive use of psychoactive drugs produces a variety of learned behaviors. These can be classified in the laboratory according to an operant/classical paradigm, but in vivo the two types of learning overlap. The classically conditioned responses produced by drugs are complex and bi-directional. There has been progress in classifying and predicting the types of conditioned responses, but little is known of mechanisms. New techniques for understanding brain function such as micro-dialysis probes in animals and advanced imaging techniques (PET and SPECT) in human subjects may be utilized in conditioning paradigms to "open the black box." Because the existence of conditioned responses in drug users is now well established, clinical studies have been instituted to determine whether modification of conditioned responses can influence clinical outcome. A recently completed study in cocaine addicts has produced evidence that outcome can be improved by a passive extinction technique over an 8-week outpatient treatment program.