The pharmacological choices for the treatment of schizophrenia have been greatly expanded with the availability of the atypical compounds clozapine (Clozaril, Novartis), risperidone (Risperdal, Janssen-Cilag), olanzapine (Zyprexa, Eli Lilly & Co.), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer Inc.) and aripiprazole (Abilify, Otsuka Pharmaceutical Co. Ltd). In this article, the effects of the newer antipsychotics and their side effects are reviewed. Key issues in acute and maintenance treatment, often lifelong, will be reviewed. Side-effect management to ensure adherence to an optimal treatment regimen will be discussed. Coexisting syndromes must be treated in concordance with the patient's clinical presentation. For treatment-resistant patients, atypical compounds are generally more effective than their typical counterparts but medication augmentation strategies are frequently recommended. Finally, the results of recent meta-analyses comparing the effects of atypical versus typical compounds will be critically reviewed and remaining gaps in the current pharmacotherapy of schizophrenia will be explored.