Although monotherapy with lithium or divalproex is the recommended initial therapy for bipolar disorder, these agents are associated with prolonged favorable outcomes in only 30% of patients. Increasingly, the medical literature is demonstrating that augmentation of mood stabilizers with atypical antipsychotics is a more effective therapy. This form of combination therapy is recommended as first-line treatment for severe bipolar mania. Recent clinical studies have shown that augmentation therapy with the atypical antipsychotics risperidone, olanzapine, quetiapine, and ziprasidone is effective in long-term maintenance treatment, and preliminary evidence is emerging that use of atypicals with mood stabilizers can help control the depressive phase of bipolar disorder. The atypical antipsychotics also have relatively mild side effect profiles, although augmentation therapy with some antipsychotics and mood stabilizers has been associated with excessive weight gain.