Bipolar II depression is characterized by the occurrence of depressive episodes in alternation with hypomanic, but not full blown manic episodes. Epidemiological studies show that it is situated on a continuum with bipolar I disorder on one side and unipolar major depressive disorder on the other side, with unclear boundaries. Various authors concluded that the treatment of bipolar II depression is unclear, poorly evidence based and thus controversial: should antidepressants be avoided as monotherapy and what is the place of lithium, anticonvulsants and atypical antipsychotics? A review of the literature shows that the risk of switch to mania/hypomania during acute treatment with antidepressants as monotherapy is smaller than in patients with bipolar I depression and that it concerns almost exclusively hypomanic switches. Therefore, there is no good evidence to avoid antidepressants as monotherapy. However, there is also no good evidence for their efficacy. Available data from a few randomized controlled trials with other drugs suggest also a place for anticonvulsants, especially lamotrigine, and for quetiapine. This is also reflected in some, but not all guidelines.