Valproate is commonly used as a first-line agent for the treatment of acute bipolar I mania. Its efficacy in the treatment of acute mania has been established in randomized, controlled trials versus placebo, lithium, haloperidol, and olanzapine. Only preliminary data regarding the efficacy of valproate in acute bipolar depression are currently available. The efficacy of valproate in the maintenance treatment of bipolar disorder has not been definitively established but most evidence from randomized, controlled trials suggests that it may have comparable efficacy to lithium and olanzapine. The results of randomized, controlled trials of valproate in the treatment of bipolar disorder are reviewed along with their implications for clinical practice.