Atypical antipsychotics have been increasingly shown to have efficacy in the treatment of various phases of bipolar disorder. Ziprasidone acts primarily through serotonergic and dopaminergic receptor antagonism, and exerts effects as an inhibitor of serotonin and norepinephrine reuptake. Ziprasidone exhibits dose proportional, linear changes in exposure and is hepatically metabolized primarily by aldehyde oxidase. In studies of patients with acute manic or mixed episodes, treatment with ziprasidone monotherapy or in combination with lithium, resulted in rapid symptom improvement and was generally well tolerated. Results from open-label extension studies of ziprasidone indicate continued improvement in manic symptoms. Preliminary data in pediatric patients with bipolar disorder also suggest it may be efficacious in this population. Ziprasidone is considered as a first-line treatment option in patients with bipolar manic or mixed episodes, with or without psychosis and displays a favorable side-effect profile.