Olanzapine (Zyprexa, Eli Lilly & Co.) is an atypical antipsychotic medication with once-daily dosing that was originally developed for the treatment of schizophrenia. It has shown broad efficacy in the treatment of bipolar mixed and manic episodes, but is less effective in the treatment of bipolar depression. Double-blind studies have demonstrated a rapid onset of action in acute bipolar mania, significantly greater rates of response compared with placebo, and a remission rate of 88.3% in a 49-week open-label study. Diverse presentations of the illness responded well to olanzapine including patients with rapid-cycling bipolar disorder, mixed episodes, as well as psychotic and nonpsychotic manias. Olanzapine monotherapy improved symptoms of depression related to its sedating and appetite-enhancing profile, but core symptoms such as depressed mood did not improve significantly. However, in combination with fluoxetine, bipolar depressed patients responded without an increased risk of mania. Weight gain and sedation are prominent adverse effects, and it has been associated with atherogenic dyslipidemia and glucose intolerance.