PURPOSE OF REVIEW: The current article attempts to summarize the current status of our knowledge and practice in the treatment of bipolar depression and suggests future directions.RECENT FINDINGS: Our knowledge about lithium solidly supports its usefulness during all phases of bipolar illness and its specific effectiveness on suicidal prevention. Specific second-generation antipsychotics could constitute a promising option for treating bipolar depression, although only limited data exist so far. Anticonvulsants appear to possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be preferably effective in the treatment of depression but not mania. The usefulness of antidepressants in bipolar depression is controversial. The first line of psychosocial intervention in bipolar depression is psychoeducation, family-focused psychoeducation and cognitive-behavioral therapy. Electroconvulsive therapy and transcranial magnetic stimulation are options for refractory patients. Accumulated knowledge so far indicates that bipolar patients need continuous administration of an antimanic agent even during the acute depressive phase.SUMMARY: The development of rationalized 'combination treatment' guidelines is essential today, as it seems that the vast majority of patients do poorly on monotherapy and need complex pharmacotherapies. Although our knowledge is indeed limited, the development of some kind of guidelines for polypharmacy is possible and should be done as soon as possible.