A growing number of uncontrolled and controlled studies performed since the mid-1960s indicate that the antiepileptic drug valproate is effective in the acute and prophylactic treatment of some patients with bipolar disorder, including those inadequately responsive to or intolerant of lithium therapy. Preliminary evidence also suggests that valproate may be particularly likely to have antimanic or mood-stabilizing effects in certain bipolar patients, including those with rapid cycling, dysphoric or mixed mania, and neurologic abnormalities. In this article, studies examining the efficacy of valproate in the treatment of bipolar disorder are reviewed and clinical guidelines for the use of valproate in bipolar patients are presented.