Mood-stabilizing drugs including lithium, anticonvulsants, and antipsychotics have established effects in the management of bipolar disorder, especially in mania. However, these drugs also have been shown to be effective in depressed patients. For example, lithium is well established as an effective augmenting strategy with tricyclic antidepressants in refractory depression. This article will review a variety of effects of mood- stabilizing drugs in bipolar and unipolar depressed patients, which will include acute treatment, prevention of relapse and recurrence, and the management of refractory patients. The effects of antipsychotics (especially atypicals) and new research directions also will be reviewed.