Abstract: Bipolar disorder is a complex condition that includes symptoms of mania, depression, and often anxiety. Diagnosing and treating bipolar depression is challenging, with the disorder often being diagnosed as unipolar depression. In addition, comorbid anxiety can be a significant detractor to successful outcomes, increasing symptom severity, frequency of episodes and suicide rates, and decreasing response to antidepressant therapy. Anxiety often precedes and hastens the onset of bipolar disorder, and a shared genetic etiology has been suggested. Studies have demonstrated the efficacy of atypical antipsychotics for the acute and maintenance treatment of mania. Evidence from studies in patients with treatment-resistant major depressive disorder and bipolar depression indicate that these agents may also have antidepressant effects. In open trials in patients with bipolar mania, risperidone therapy has led to significant reductions in depression scores compared with baseline. Reductions in depression scores in patients with bipolar mania have been significantly greater with olanzapine compared with placebo. In patients with bipolar depression, the combination of olanzapine and fluoxetine resulted in significant improvement in depression compared with olanzapine alone or placebo. Although little data are available on the effects of these agents on comorbid anxiety in patients with bipolar disorder, some atypical antipsychotics have demonstrated efficacy in patients with anxiety disorders, including obsessive-compulsive disorder, post-traumatic stress disorder, and generalized anxiety disorder. Thus, atypical antipsychotics represent an important therapeutic option for the treatment of bipolar disorder, providing improvements in manic, depressive, and anxiety symptoms.