Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are atypical antipsychotics approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia and bipolar disorder. These drugs have been studied for off-label use in the following conditions: dementia and severe geriatric agitation, depression, obsessive-compulsive disorder, posttraumatic stress disorder, and personality disorders. The atypicals have also been studied for the management of Tourette’s syndrome and autism in children. The purpose of this report is to review the scientific evidence on the safety and effectiveness of such off-label uses.