Schizophrenia, a chronic mental disorder, has a lifetime prevalence rate of approximately 1%. The first antipsychotic drug, chlorpromazine, was introduced in 1954, followed by several similar drugs. With the introduction of clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and more recently paliperidone, iloperidone, asenapine, and lurasidone, antipsychotic drugs are often classified as first generation or typical (chlorpromazine-like) versus second generation or atypical (clozapine-like), although the distinction between the two classes, particularly with respect to efficacy, is not as meaningful as initially believed. Both classes have been demonstrated to safely improve psychotic symptoms in the acute phase of the illness and to reduce the risk of relapse in the maintenance phase of treatment. Because of the limited efficacy of antipsychotics in resolving the full range of schizophrenic psychopathology, adjunctive treatments are often used to reduce morbidity. This chapter reviews controlled trials of the pharmacological agents used to treat schizophrenia.