With the emergence of specific pharmacological probes for various serotonin (5-HT) receptors and radio-ligands for central 5-HT, it has now become possible to investigate its role in the pathogenesis of bipolar disorder more closely. This paper critically reviews the scientific literature regarding the relationship between bipolar disorder and serotonergic systems. The evidence suggests that central serotonergic activity is reduced in the depressive phase of bipolar disorder. Similar findings have been reported in bipolar patients when euthymic, indicating that that lower 5-HT activity could be a trait marker for bipolar disorder. Findings reported in the manic phase of this illness are inconsistent.