Besides maintaining long-term stability, the most difficult aspect in the management of bipolar affective disorder is the depressive phase. The similarities in the cluster of symptoms with unipolar depression, as well as factors related to the patient, psychiatrist and the treatment itself could make the tasks of diagnosing and treating bipolar depression extremely challenging. A lack of clear guidance makes the choice of medication even harder, especially with the presence of conflicting recommendations. In this review we will explore the evidence base for available medication options, from antidepressants, lithium, anticonvulsants and antipsychotics as well as from other groups. However, any conclusions and guidance still suffer from some degree of uncertainty due to the limitations of evidence for some drugs, especially the relative lack of head-to-head comparisons.