The prevalence of substance abuse is elevated among schizophrenic patients. When free of illicit substances and sober, substance-abusing schizophrenic patients may have a better prognosis than other frequently hospitalized schizophrenic patients. However, the cost of substance abuse is great in terms of rehospitalization, homelessness, risk of other medical illness, disruption of social and vocational function, exacerbation of symptoms, suicide, and increased health care expenses. Important recent developments in medications for reducing substance abuse in nonschizophrenic populations make it timely to consider factors that might contribute to substance abuse among schizophrenic patients. This review will focus on substances most frequently abused by schizophrenic patients: nicotine, alcohol, cannabis, and psychostimulants. It concentrates on two conceptual foci: "self-medication hypotheses" and "comorbid addiction vulnerability hypotheses". The relationship between these hypotheses and possible pharmacotherapeutic approaches for substance-abusing schizophrenic patients will be considered.