Ziprasidone is a second generation (“atypical”) antipsychotic drug that has been used alone and as an adjunct to standard mood stabilizers to reduce recurrence rates in bipolar disorder. Approval of ziprasidone as an adjunct to lithium or valproate in 2009 was based on an industry sponsored study of 584 outpatients with a current or recent manic episode; 240 of these subjects were randomized to adjunctive ziprasidone or placebo and 138 completed a six month trial. Patients enrolled in maintenance studies did not have refractory mood disorders, comorbid conditions or risk of dangerousness. Maintenance ziprasidone augmentation is an option for patients who do not respond to a single mood stabilizer rapidly, and possibly for those with residual psychotic symptoms, but there are insufficient data to prefer this approach to combinations of mood stabilizers or augmentation with other agents. Ziprasidone is generally well tolerated, with less sedation and weight gain than many other antipsychotic drugs; it should be taken with food. Primary interactions of concern are with other serotonergic medications, MAO inhibitors, and other medications that prolong the QT interval.