Bipolar depression, and particularly its long-term treatment, represents a challenge nowadays. Although mania and hypomania are the distinctive mood disturbances in bipolar disorder, it is becoming increasingly apparent that depression is the predominant mood alteration in bipolar disorder, and the main cause of dysfunction and mortality for patients. However, despite the clear clinical and public health implications of these facts, research has traditionally neglected bipolar depression, and clinicians continue to encounter many difficulties in the management of patients. Lithium and anticonvulsants, with the exception of lamotrigine, appear to be more effective in mania than in depression. Antidepressants, particularly tricyclics and dual acting compounds, may induce mania, especially when used in the absence of an antimanic drug. The evidence on this safety concern is less compelling as far as SSRIs are concerned. Changes in dopaminergic activity have been implicated in the pathogenesis of bipolar depression and now two apparently opposite strategies are being used to improve depressive symptoms in bipolar patients: adjunctive dopamine agonists, such as pramipexole, or dopamine antagonists, such as atypical antipsychotics. Three recent placebo-controlled studies support the use of olanzapine, and particularly quetiapine, in the treatment of bipolar depressed patients. Electroconvulsive therapy remains as an option in treatment-resistant patients. Cognitive-behavioral therapy and psychoeducation seem much better for the prevention of relapse than for the treatment of acute episodes. Further studies are ongoing to test novel strategies for the long-term treatment of bipolar depression.