Most individuals with schizophrenia have problems with abuse of substances ranging from licit substances, such as nicotine, to illicit ones, such as cocaine. This comorbidity may reflect self-medication, as well as a biological susceptibility to both disorders. Twin studies have suggested that this biological susceptibility may involve genetic factors. Other biological risk factors may involve the medications used to treat schizophrenia, which may produce symptoms that provoke abuse of drugs to relieve negative symptoms or may even enhance the euphoric response to abused drugs. The articles in this issue address several research areas related to substance abuse and schizophrenia, including the differential diagnosis of schizophrenia and organic disorders induced by substance abuse and the impact of substance abuse on the course of early schizophrenia. The management of substance-abusing schizophrenia patients requires a careful balance of pharmacotherapy and psychotherapies, and atypical antipsychotic agents may be particularly helpful. Psychotherapy needs to focus both on the management of affect and on the adequate monitoring of drug abstinence.