Ziprasidone (CP-88059) is an atypical, or second-generation, antipsychotic agent that has demonstrated activity for treating positive, negative, cognitive, and affective symptoms of schizophrenia and schizoaffective disorder and for treating mania and mixed states in bipolar disorder, with limited adverse extrapyramidal, sedative, anticholinergic, and cardiometabolic effects. Ziprasidone was first synthesized on the Pfizer Central Research campus in Groton, Connecticut. Both the oral and intramuscular formulations of this antipsychotic were initially part of a new drug application for the treatment of psychotic disorders submitted to the U.S. Food and Drug Administration (FDA) under the product name Zeldox in 1997. Because of concerns regarding an observed increase in the mean duration of the QT interval, an electrocardiographic measure of the ventricular depolarization and repolarization phases of cardiac conduction, the application was not initially approved. Further studies, designed in collaboration with the FDA, quantified the limited extent of this effect seen with ziprasidone compared with the effect seen with other agents in wide use; these studies established an approvable level of safety for ziprasidone with respect to cardiac conduction and a benchmark for the approach to evaluating drug effects on the QT interval that has subsequently been applied to other agents evaluated by the FDA. The FDA approved oral ziprasidone in February 2001 under the trade name Geodon for the treatment of schizophrenia. The intramuscular formulation received FDA approval in 2002 for the treatment of acute agitation due to schizophrenia. In August 2004, oral ziprasidone received FDA approval for the treatment of bipolar mania, including manic and mixed episodes. At the time of writing, ziprasidone has received regulatory approval and is available in over 70 countries, usually under the trade name Zeldox, with more than 1.08 million patient-years of drug exposure.