Unmedicated schizophrenia patients relapse at a rate of approximately 10% per month. Maintenance treatment with antipsychotic medications can reduce this rate dramatically. Ensuring compliance with medication in the maintenance treatment of schizophrenia encompasses 3 areas of concern: (1) choice of antipsychotic medication, accounting for efficacy and side effects; (2) route of administration of medications, considering the benefits and detriments of long-acting injectable and oral medications; and (3) reducing "doctor noncompliance," the failure of some physicians to perceive the need for long-term treatment for patients with chronic schizophrenia. This article focuses on the selection of the antipsychotic medication that will most likely lead to successful maintenance treatment of schizophrenia. Data from acute trials must be relied upon to evaluate the comparative risks and benefits of these agents as long-term treatments since few double-blind, random-assignment studies have compared the newer-generation antipsychotics for maintenance treatment of schizophrenia. Studies of acute treatment, as well as a small number of studies of maintenance treatment, have shown the newer-generation antipsychotics risperidone and olanzapine to be more efficacious and to have a more favorable side effect profile than conventional-generation antipsychotics. Research on the newer-generation antipsychotics, including ziprasidone, aripiprazole, and quetiapine, shows these agents to be efficacious and safe, although the limited amount of data on these agents precludes a definitive evaluation of their efficacy and safety.