Olanzapine is currently marketed not only for the treatment of schizophrenia, but also for the treatment of acute mania and the prevention of relapse in patients successfully treated with this drug for a manic episode. A large body of good clinical trials supports these indications. In the mania trials, olanzapine was more efficacious than placebo, equal or more efficacious than valproate and more efficacious than lithium or valproate monotherapy when used in combination with either drug. A trial that compared olanzapine with haloperidol failed to show superiority of the atypical versus the conventional. Olanzapine showed a modest but statistically significant effect in the treatment of bipolar depression; this modest effect was substantially enhanced in combination with fluoxetine. The long-term trials showed that olanzapine was better than placebo in the prevention of manic and depressive relapse and not inferior to lithium or valproate. The combination of olanzapine with lithium or valproate was also more efficacious than lithium or valproate alone in the prevention of manic relapse in patients partially non-responding to monotherapy with lithium or valproate. All these trials suggest that olanzapine may be a valuable drug in the short- and long-term treatment of bipolar I disorder. However, there are some concerns about the safety and tolerability of olanzapine in this population, as far as weight gain and metabolic syndrome are concerned, which may be addressed in future pharmacovigilance studies.