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 classical CRs produced by drugs are complex and bidirectional. There has been progress in classifying and predicting the types of CRs, but little is known of mechanisms. New techniques for understanding brain function, such as microdialysis probes in animals and advanced imaging techniques (positron emission tomography and single photon emission computerized tomography) in human subjects, may be utilized in conditioning paradigms to "open the black box." Because the existence of CRs in drug users is now well established, clinical studies have been instituted to determine whether modification of CRs 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.